Pub Date : 2001-05-01DOI: 10.1097/00008877-200105000-00001
C. Belzung, A.M. Le Guisquet, S. Barreau, F. Calatayud
Although selective 5‐hydroxytryptamine (5‐HT) reuptake inhibitors (SSRIs) are widely used in the chronic treatment of several anxiety disorders, increased anxiety has been observed in some patients at the beginning of treatment with these compounds. Similar increases in anxiety‐related behaviors have been observed in animal studies following a single injection with SSRIs. The mechanism underlying this effect is unclear. The aim of the present study was to investigate the effects of a variety of psychoactive compounds on the anxiogenic‐like activity of fluoxetine. The drugs used included the benzodiazepine diazepam, the 5‐HT 1A receptor partial agonist buspirone, the 5‐HT 1A receptor antagonists pindolol and WAY‐100635, the non‐selective 5‐HT 2 receptor antagonists methiothepin, mianserin and ritanserin, the non‐selective dopamine (DA) receptor antagonist haloperidol, the D 1 antagonist SCH23390, the selective D 2 antagonist raclopride, the D 2/3 agonist quinelorane, the cholecystokinin B (CCK B ) receptor antagonist LY 288513, and the corticotropin‐releasing factor 1 (CRF 1 ) receptor antagonist CP‐154,526. Experiments were performed in the free‐exploration test. This model is based on the strong neophobic reactions exhibited by BALB/c mice when confronted simultaneously with a familiar and a novel environment. When administered alone, diazepam (1 and 2 mg/kg), buspirone (1 mg/kg) and mianserin (0.3 mg/kg) produced anxiolytic‐like effects as they significantly increased exploratory activity of the novel compartment. In contrast, fluoxetine (20 mg/kg) almost completely suppressed exploration of the novel area. Diazepam reversed the anxiogenic‐like as well as the locomotor impairment induced by fluoxetine, while quinelorane blocked only the anxiogenic action of fluoxetine. None of the other compounds was able to counteract this effect. Taken together, these results suggest that dopaminergic mechanisms may underlie, at least in part, the behavioral effects of fluoxetine in the free‐exploration test, whereas 5‐HT 1A , 5‐HT 2 , CCK B and CRF 1 receptors may not be involved primarily in these effects.
{"title":"An investigation of the mechanisms responsible for acute fluoxetine‐induced anxiogenic‐like effects in mice","authors":"C. Belzung, A.M. Le Guisquet, S. Barreau, F. Calatayud","doi":"10.1097/00008877-200105000-00001","DOIUrl":"https://doi.org/10.1097/00008877-200105000-00001","url":null,"abstract":"Although selective 5‐hydroxytryptamine (5‐HT) reuptake inhibitors (SSRIs) are widely used in the chronic treatment of several anxiety disorders, increased anxiety has been observed in some patients at the beginning of treatment with these compounds. Similar increases in anxiety‐related behaviors have been observed in animal studies following a single injection with SSRIs. The mechanism underlying this effect is unclear. The aim of the present study was to investigate the effects of a variety of psychoactive compounds on the anxiogenic‐like activity of fluoxetine. The drugs used included the benzodiazepine diazepam, the 5‐HT 1A receptor partial agonist buspirone, the 5‐HT 1A receptor antagonists pindolol and WAY‐100635, the non‐selective 5‐HT 2 receptor antagonists methiothepin, mianserin and ritanserin, the non‐selective dopamine (DA) receptor antagonist haloperidol, the D 1 antagonist SCH23390, the selective D 2 antagonist raclopride, the D 2/3 agonist quinelorane, the cholecystokinin B (CCK B ) receptor antagonist LY 288513, and the corticotropin‐releasing factor 1 (CRF 1 ) receptor antagonist CP‐154,526. Experiments were performed in the free‐exploration test. This model is based on the strong neophobic reactions exhibited by BALB/c mice when confronted simultaneously with a familiar and a novel environment. When administered alone, diazepam (1 and 2 mg/kg), buspirone (1 mg/kg) and mianserin (0.3 mg/kg) produced anxiolytic‐like effects as they significantly increased exploratory activity of the novel compartment. In contrast, fluoxetine (20 mg/kg) almost completely suppressed exploration of the novel area. Diazepam reversed the anxiogenic‐like as well as the locomotor impairment induced by fluoxetine, while quinelorane blocked only the anxiogenic action of fluoxetine. None of the other compounds was able to counteract this effect. Taken together, these results suggest that dopaminergic mechanisms may underlie, at least in part, the behavioral effects of fluoxetine in the free‐exploration test, whereas 5‐HT 1A , 5‐HT 2 , CCK B and CRF 1 receptors may not be involved primarily in these effects.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"16 1","pages":"151-162"},"PeriodicalIF":0.0,"publicationDate":"2001-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85244236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-05-01DOI: 10.1097/00008877-200105000-00008
M. Rodrı´guez‐Arias, J. Miñarro, V. Simón
Many reports have demonstrated that there is a development of tolerance to many effects produced by morphine. This study was conducted with the aim of determining whether the antiaggressive actions of morphine develop tolerance after chronic administration. Acute morphine administration produced antiaggressive effects which disappeared after chronic (7 days) treatment in isolated mice. An increase in non‐social exploration was observed, representing morphine‐induced hyperactivity, after acute treatment, which was not present after chronic administration. In conclusion, there is a development of tolerance to the antiaggressive and motor effects of morphine.
{"title":"Development of tolerance to the antiaggressive effects of morphine","authors":"M. Rodrı´guez‐Arias, J. Miñarro, V. Simón","doi":"10.1097/00008877-200105000-00008","DOIUrl":"https://doi.org/10.1097/00008877-200105000-00008","url":null,"abstract":"Many reports have demonstrated that there is a development of tolerance to many effects produced by morphine. This study was conducted with the aim of determining whether the antiaggressive actions of morphine develop tolerance after chronic administration. Acute morphine administration produced antiaggressive effects which disappeared after chronic (7 days) treatment in isolated mice. An increase in non‐social exploration was observed, representing morphine‐induced hyperactivity, after acute treatment, which was not present after chronic administration. In conclusion, there is a development of tolerance to the antiaggressive and motor effects of morphine.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"59 1","pages":"221-224"},"PeriodicalIF":0.0,"publicationDate":"2001-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74376971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-05-01DOI: 10.1097/00008877-200105000-00004
M. Field, T. Duka
Smokers’ responses to smoking cues may be the result of a classical conditioning process. There is evidence that classical conditioning may not proceed in human subjects unless subjects are consciously aware of the stimulus (CS)–reinforcer (UCS) contingencies. In two experiments the role of CS↔UCS contingency awareness in the expression of conditioned responses (craving, salivation, and skin conductance) was studied. A discriminative classical conditioning paradigm was used during which subjects were presented with one stimulus (the CS+) always paired with cigarette smoking (the UCS) and another (the CS−) never paired with cigarette smoking. Half of the subjects were given instructions to discover the CS↔UCS contingencies (group ‘aware’, AWR), whereas the other half were not (group ‘unaware’, UWR). In experiment 1, all subjects responded to the CS+ with increased cigarette craving relative to the CS−; this effect was more pronounced in the AWR group compared to the UWR group. A lower amount of salivation in response to the CS+ compared to the CS− was found in the UWR group. These between‐group differences were interpreted as a consequence of the enhanced expectancies of smoking in the presence of CS+ in group AWR compared to group UWR. In experiment 2, the observed craving responses to CS+ and CS− were consistent with those seen in experiment 1, but no discriminative salivary response to the stimuli was found. When, after conditioning training, subjects’ expectancies of smoking were removed by instructions, and their responses to CS+ and CS− were again measured, the discriminative craving response to CS+ and CS− was eliminated and all subjects demonstrated a lower amount of salivation in response to the CS+ compared to the CS−. These data suggest that presentation of arbitrary cues previously paired with cigarette smoking can elicit CRs and that facilitation of awareness of the CS↔UCS contingency by instructions can potentiate craving CRs. In addition, these data suggest that craving CRs can be eliminated, whereas compensatory CRs can be facilitated, when cigarette expectancy is removed with instructions.
{"title":"Smoking expectancy mediates the conditioned responses to arbitrary smoking cues","authors":"M. Field, T. Duka","doi":"10.1097/00008877-200105000-00004","DOIUrl":"https://doi.org/10.1097/00008877-200105000-00004","url":null,"abstract":"Smokers’ responses to smoking cues may be the result of a classical conditioning process. There is evidence that classical conditioning may not proceed in human subjects unless subjects are consciously aware of the stimulus (CS)–reinforcer (UCS) contingencies. In two experiments the role of CS↔UCS contingency awareness in the expression of conditioned responses (craving, salivation, and skin conductance) was studied. A discriminative classical conditioning paradigm was used during which subjects were presented with one stimulus (the CS+) always paired with cigarette smoking (the UCS) and another (the CS−) never paired with cigarette smoking. Half of the subjects were given instructions to discover the CS↔UCS contingencies (group ‘aware’, AWR), whereas the other half were not (group ‘unaware’, UWR). In experiment 1, all subjects responded to the CS+ with increased cigarette craving relative to the CS−; this effect was more pronounced in the AWR group compared to the UWR group. A lower amount of salivation in response to the CS+ compared to the CS− was found in the UWR group. These between‐group differences were interpreted as a consequence of the enhanced expectancies of smoking in the presence of CS+ in group AWR compared to group UWR. In experiment 2, the observed craving responses to CS+ and CS− were consistent with those seen in experiment 1, but no discriminative salivary response to the stimuli was found. When, after conditioning training, subjects’ expectancies of smoking were removed by instructions, and their responses to CS+ and CS− were again measured, the discriminative craving response to CS+ and CS− was eliminated and all subjects demonstrated a lower amount of salivation in response to the CS+ compared to the CS−. These data suggest that presentation of arbitrary cues previously paired with cigarette smoking can elicit CRs and that facilitation of awareness of the CS↔UCS contingency by instructions can potentiate craving CRs. In addition, these data suggest that craving CRs can be eliminated, whereas compensatory CRs can be facilitated, when cigarette expectancy is removed with instructions.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"355 1","pages":"183-194"},"PeriodicalIF":0.0,"publicationDate":"2001-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75453439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-05-01DOI: 10.1097/00008877-200105000-00005
D. McMillan, W. Hardwick, Mi Li
Pigeons were trained to discriminate among 5 mg/kg pentobarbital, 10 mg/kg pentobarbital, and saline, under either fixed‐interval (FI) or fixed‐ratio (FR) reinforcement schedules. When baseline responding stabilized, a higher percentage of responses occurred on the key that produced the reinforcer under the FR schedule than under the FI schedule. After low doses of pentobarbital, responding shifted from the saline key to the 5 mg/kg pentobarbital key; at higher doses of pentobarbital responding shifted to the 10 mg/kg pentobarbital key under both schedules. After low doses of ethanol and chlordiazepoxide, responding shifted from the saline key to the 5 mg/kg pentobarbital key, but after high doses of these drugs, responding continued to occur on the 5 mg/kg pentobarbital key under both reinforcement schedules. A 5 mg/kg dose of pentobarbital increased responding on the 10 mg/kg pentobarbital key when it was combined with pentobarbital, ethanol or chlordiazepoxide. Phencyclidine and d ‐amphetamine produced responding largely on the saline key under both reinforcement schedules. Under the FR schedule, pentobarbital dose–response curves were usually quantal, whereas under the FI schedule the pentobarbital dose–response curves usually were graded.
{"title":"Discrimination of pentobarbital doses and drug mixtures under fixed‐ratio and fixed‐interval reinforcement schedules","authors":"D. McMillan, W. Hardwick, Mi Li","doi":"10.1097/00008877-200105000-00005","DOIUrl":"https://doi.org/10.1097/00008877-200105000-00005","url":null,"abstract":"Pigeons were trained to discriminate among 5 mg/kg pentobarbital, 10 mg/kg pentobarbital, and saline, under either fixed‐interval (FI) or fixed‐ratio (FR) reinforcement schedules. When baseline responding stabilized, a higher percentage of responses occurred on the key that produced the reinforcer under the FR schedule than under the FI schedule. After low doses of pentobarbital, responding shifted from the saline key to the 5 mg/kg pentobarbital key; at higher doses of pentobarbital responding shifted to the 10 mg/kg pentobarbital key under both schedules. After low doses of ethanol and chlordiazepoxide, responding shifted from the saline key to the 5 mg/kg pentobarbital key, but after high doses of these drugs, responding continued to occur on the 5 mg/kg pentobarbital key under both reinforcement schedules. A 5 mg/kg dose of pentobarbital increased responding on the 10 mg/kg pentobarbital key when it was combined with pentobarbital, ethanol or chlordiazepoxide. Phencyclidine and d ‐amphetamine produced responding largely on the saline key under both reinforcement schedules. Under the FR schedule, pentobarbital dose–response curves were usually quantal, whereas under the FI schedule the pentobarbital dose–response curves usually were graded.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"48 1","pages":"195-208"},"PeriodicalIF":0.0,"publicationDate":"2001-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75862430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-04-01DOI: 10.1097/00008877-200104000-00002
M. Nader, D. Morgan
Although punishment contingencies are widely used with human drug users, basic research on the effectiveness of these procedures is limited. The present study evaluated the effects of a negative punishment contingency, response‐contingent timeout (TO) presentation, on cocaine‐maintained responding. Rhesus monkeys were trained under a multiple fixed interval (FI) 5‐min cocaine, conjoint FI 5‐min cocaine‐variable‐interval (VI) 30‐sec TO schedule. TO values were either 0 (baseline), 10, 30, or 60 s in length. During the TO periods, the FI clock continued to operate but the discriminative stimuli signaling cocaine availability were removed, and responding had no scheduled consequence. Cocaine maintained responding in all monkeys and the dose–effect curve was characterized as an inverted U‐shaped function. The response‐contingent TO presentations reduced response rates maintained by cocaine in all monkeys compared to baseline. The magnitude of the reduction in response rates was not a function of the length of the TO period (i.e. intensity of the punisher), and the punishment effect was enhanced by increases in cocaine dose. When responding was punished, response rates in the unpunished components either also decreased (i.e. response induction; ∼30% of the cases) or were not affected (∼60%). These results demonstrate that cocaine‐maintained behavior can be decreased by environmental manipulations involving negative punishment contingencies.
{"title":"Effects of negative punishment contingencies on cocaine self‐administration by rhesus monkeys","authors":"M. Nader, D. Morgan","doi":"10.1097/00008877-200104000-00002","DOIUrl":"https://doi.org/10.1097/00008877-200104000-00002","url":null,"abstract":"Although punishment contingencies are widely used with human drug users, basic research on the effectiveness of these procedures is limited. The present study evaluated the effects of a negative punishment contingency, response‐contingent timeout (TO) presentation, on cocaine‐maintained responding. Rhesus monkeys were trained under a multiple fixed interval (FI) 5‐min cocaine, conjoint FI 5‐min cocaine‐variable‐interval (VI) 30‐sec TO schedule. TO values were either 0 (baseline), 10, 30, or 60 s in length. During the TO periods, the FI clock continued to operate but the discriminative stimuli signaling cocaine availability were removed, and responding had no scheduled consequence. Cocaine maintained responding in all monkeys and the dose–effect curve was characterized as an inverted U‐shaped function. The response‐contingent TO presentations reduced response rates maintained by cocaine in all monkeys compared to baseline. The magnitude of the reduction in response rates was not a function of the length of the TO period (i.e. intensity of the punisher), and the punishment effect was enhanced by increases in cocaine dose. When responding was punished, response rates in the unpunished components either also decreased (i.e. response induction; ∼30% of the cases) or were not affected (∼60%). These results demonstrate that cocaine‐maintained behavior can be decreased by environmental manipulations involving negative punishment contingencies.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"102 1","pages":"91-99"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81836630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-02-01DOI: 10.1097/00008877-200102000-00007
D. Kunin, S. Gaskin, M. Borjas, B. R. Smith, Z. Amit
Differences in locomotor response to an inescapable novel environment have previously been shown to predict sensitivity to amphetamine reward, where high responders (HR), compared to low responders (LR), showed greater initial sensitivity to amphetamine self-administration. The present experiments sought to extend these findings and assessed the relationship between locomotor response to an inescapable novel environment and conditioned taste aversion (CTA) with amphetamine and lithium chloride (LiCl). Male Sprague–Dawley rats were tested for their locomotor response to an inescapable novel environment and divided into high (HR) or low (LR) responders, based on whether their locomotor scores were above or below the median activity level of the subject sample. After several days, the animals were tested in a CTA procedure and conditioned with either amphetamine or lithium chloride. Compared to HR rats, LR rats showed greater sensitivity to amphetamine CTA at the doses tested. In contrast, the results with LiCl showed no relationship between locomotor response to an inescapable novel environment and CTA. Taken together, the present results suggest that LR, compared to HR, rats show less sensitivity to the rewarding effects of amphetamine because they are more sensitive to aversive effects of amphetamine, as reflected in CTA. In contrast, HR rats display less sensitivity to aversive effects of amphetamine, which may explain their greater propensity to self-administer amphetamine.
{"title":"Differences in locomotor response to an inescapable novel environment predict sensitivity to aversive effects of amphetamine","authors":"D. Kunin, S. Gaskin, M. Borjas, B. R. Smith, Z. Amit","doi":"10.1097/00008877-200102000-00007","DOIUrl":"https://doi.org/10.1097/00008877-200102000-00007","url":null,"abstract":"Differences in locomotor response to an inescapable novel environment have previously been shown to predict sensitivity to amphetamine reward, where high responders (HR), compared to low responders (LR), showed greater initial sensitivity to amphetamine self-administration. The present experiments sought to extend these findings and assessed the relationship between locomotor response to an inescapable novel environment and conditioned taste aversion (CTA) with amphetamine and lithium chloride (LiCl). Male Sprague–Dawley rats were tested for their locomotor response to an inescapable novel environment and divided into high (HR) or low (LR) responders, based on whether their locomotor scores were above or below the median activity level of the subject sample. After several days, the animals were tested in a CTA procedure and conditioned with either amphetamine or lithium chloride. Compared to HR rats, LR rats showed greater sensitivity to amphetamine CTA at the doses tested. In contrast, the results with LiCl showed no relationship between locomotor response to an inescapable novel environment and CTA. Taken together, the present results suggest that LR, compared to HR, rats show less sensitivity to the rewarding effects of amphetamine because they are more sensitive to aversive effects of amphetamine, as reflected in CTA. In contrast, HR rats display less sensitivity to aversive effects of amphetamine, which may explain their greater propensity to self-administer amphetamine.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"17 1","pages":"61-67"},"PeriodicalIF":0.0,"publicationDate":"2001-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82756123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-02-01DOI: 10.1097/00008877-200102000-00005
N. Swerdlow, A. Eastvold, K. Uyan, Y. Ploum, K. Cadenhead
Prepulse inhibition (PPI), a measure of sensorimotor gating, is impaired in certain neuropsychiatric disorders. Animal studies have revealed drug effects on PPI that may be relevant to understanding the biology of gating deficits in human populations. Recent efforts have examined similarities and differences in drug effects on PPI between rodents and humans. Experimental designs are needed that most effectively translate these drug studies across species. In the course of a larger set of studies of drug effects on startle in normal human subjects, we examined the potential utility of one design element that is utilized in rodent PPI drug studies: pre-testing to diminish variability across dose groups. Startle was measured during a screening session; 7–10 days later, 20 subjects were retested after consuming a placebo pill. Acoustic and tactile startle, and unimodal and cross-modal PPI, were measured in five sessions over a period of 3 hours post-placebo. There were significant and robust correlations between levels of startle magnitude and PPI during pre-testing and testing, for both left and right eyeblink measures. Comparable correlations were evident for both unimodal and cross-modal testing. Pre-testing values were most predictive of test performance early in the 3-hour test session, and predictive strength diminished or disappeared towards the end of testing. The utility of a pre-testing design could be seen clearly by comparing groups ‘matched’, based on pre-test data, versus groups created by alternating or random group assignments. It is concluded that pre-test designs can effectively match groups with comparable levels of startle or PPI, and thereby diminish between-group variability in human PPI drug studies. For studies using repeated testing to assess drug time course, the predictive value of pre-testing is greatest in early test sessions.
{"title":"Matching strategies for drug studies of prepulse inhibition in humans","authors":"N. Swerdlow, A. Eastvold, K. Uyan, Y. Ploum, K. Cadenhead","doi":"10.1097/00008877-200102000-00005","DOIUrl":"https://doi.org/10.1097/00008877-200102000-00005","url":null,"abstract":"Prepulse inhibition (PPI), a measure of sensorimotor gating, is impaired in certain neuropsychiatric disorders. Animal studies have revealed drug effects on PPI that may be relevant to understanding the biology of gating deficits in human populations. Recent efforts have examined similarities and differences in drug effects on PPI between rodents and humans. Experimental designs are needed that most effectively translate these drug studies across species. In the course of a larger set of studies of drug effects on startle in normal human subjects, we examined the potential utility of one design element that is utilized in rodent PPI drug studies: pre-testing to diminish variability across dose groups. Startle was measured during a screening session; 7–10 days later, 20 subjects were retested after consuming a placebo pill. Acoustic and tactile startle, and unimodal and cross-modal PPI, were measured in five sessions over a period of 3 hours post-placebo. There were significant and robust correlations between levels of startle magnitude and PPI during pre-testing and testing, for both left and right eyeblink measures. Comparable correlations were evident for both unimodal and cross-modal testing. Pre-testing values were most predictive of test performance early in the 3-hour test session, and predictive strength diminished or disappeared towards the end of testing. The utility of a pre-testing design could be seen clearly by comparing groups ‘matched’, based on pre-test data, versus groups created by alternating or random group assignments. It is concluded that pre-test designs can effectively match groups with comparable levels of startle or PPI, and thereby diminish between-group variability in human PPI drug studies. For studies using repeated testing to assess drug time course, the predictive value of pre-testing is greatest in early test sessions.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"26 1","pages":"45-52"},"PeriodicalIF":0.0,"publicationDate":"2001-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83703707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-02-01DOI: 10.1097/00008877-200102000-00004
Kenneth A. Perkins, C. Fonte, J. Meeker, W. White, A. Wilson
Smokers often report that the first cigarette of the day is the most rewarding, and subsequent smoking is less rewarding. Reduction in smoking enjoyment later in the day may be related to acute tolerance to the discriminative stimulus effects of nicotine. We examined changes in nicotine discrimination behaviour in humans as a function of acute nicotine pretreatment. Male and female dependent smokers (n = 15) were initially trained to discriminate 20 μg/kg nicotine by nasal spray from placebo (0 μg/kg) without nicotine pretreatment. They then were tested on generalization of discrimination across a range of spray doses from 0–20 μg/kg following pretreatment with placebo, moderate dose (14–21 mg) or high dose (28–42 mg) transdermal nicotine. Generalization testing involved both two- and three-response (‘novel’ option) quantitative procedures. Subjects also engaged in a self-administration phase at the end of each session, involving choices between nicotine (20 μg/kg) and placebo spray. Nicotine pretreatment significantly attenuated nicotine-appropriate responding at higher nicotine spray doses, suggesting acute tolerance, but only in women. Similar results were seen for subjective ‘head rush’, suggesting this effect may be related to discrimination behaviour in women. However, nicotine pretreatment also increased novel-appropriate responding, especially in men, following intermediate generalization doses, suggesting qualitatively different stimulus effects. Although differences were not significant, nicotine self-administration tended to be inversely associated with nicotine pretreatment dose in men but not in women. These results only modestly support the notion of acute tolerance to the discriminative stimulus effects of nicotine, and even then only in women and not in men.
{"title":"The discriminative stimulus and reinforcing effects of nicotine in humans following nicotine pretreatment","authors":"Kenneth A. Perkins, C. Fonte, J. Meeker, W. White, A. Wilson","doi":"10.1097/00008877-200102000-00004","DOIUrl":"https://doi.org/10.1097/00008877-200102000-00004","url":null,"abstract":"Smokers often report that the first cigarette of the day is the most rewarding, and subsequent smoking is less rewarding. Reduction in smoking enjoyment later in the day may be related to acute tolerance to the discriminative stimulus effects of nicotine. We examined changes in nicotine discrimination behaviour in humans as a function of acute nicotine pretreatment. Male and female dependent smokers (n = 15) were initially trained to discriminate 20 μg/kg nicotine by nasal spray from placebo (0 μg/kg) without nicotine pretreatment. They then were tested on generalization of discrimination across a range of spray doses from 0–20 μg/kg following pretreatment with placebo, moderate dose (14–21 mg) or high dose (28–42 mg) transdermal nicotine. Generalization testing involved both two- and three-response (‘novel’ option) quantitative procedures. Subjects also engaged in a self-administration phase at the end of each session, involving choices between nicotine (20 μg/kg) and placebo spray. Nicotine pretreatment significantly attenuated nicotine-appropriate responding at higher nicotine spray doses, suggesting acute tolerance, but only in women. Similar results were seen for subjective ‘head rush’, suggesting this effect may be related to discrimination behaviour in women. However, nicotine pretreatment also increased novel-appropriate responding, especially in men, following intermediate generalization doses, suggesting qualitatively different stimulus effects. Although differences were not significant, nicotine self-administration tended to be inversely associated with nicotine pretreatment dose in men but not in women. These results only modestly support the notion of acute tolerance to the discriminative stimulus effects of nicotine, and even then only in women and not in men.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"36 1","pages":"35-44"},"PeriodicalIF":0.0,"publicationDate":"2001-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89784166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-02-01DOI: 10.1097/00008877-200102000-00002
C. Murphy, C. Heidbreder, J. Feldon,
Psychostimulant‐induced locomotor sensitization and disrupted latent inhibition (LI) of a classically conditioned association are two paradigms that have been widely studied as animal behavioural models of psychosis. In this study we assessed the effects of withdrawal from the repeated intermittent administration of cocaine on LI of a conditioned fear response. Animals which were either preexposed (PE) to a tone conditioned stimulus (CS) or naive to the tone (i.e. non‐preexposed: NPE) subsequently experienced 10 pairings of the tone CS with footshock. Afterwards, both groups received five daily injections of cocaine (20 mg/kg, i.p.) or saline. After 3 days of withdrawal from drug treatment, animals were tested for conditioned freezing to the context of the footshock chamber, and 1 day later, for conditioned freezing to the tone CS. Cocaine‐sensitized animals exhibited markedly enhanced LI compared to saline‐treated animals, due to the fact that NPE–cocaine animals spent more time freezing during the tone CS than NPE–saline animals, whereas PE–cocaine animals showed a tendency toward reduced freezing compared to the saline groups. While these results suggest the presence of increased anxiety in cocaine‐withdrawn NPE animals, the absence of this effect in cocaine‐withdrawn PE rats indicates that cocaine withdrawal also influences the retrieval of previously learned information.
{"title":"Acute withdrawal from repeated cocaine treatment enhances latent inhibition of a conditioned fear response","authors":"C. Murphy, C. Heidbreder, J. Feldon,","doi":"10.1097/00008877-200102000-00002","DOIUrl":"https://doi.org/10.1097/00008877-200102000-00002","url":null,"abstract":"Psychostimulant‐induced locomotor sensitization and disrupted latent inhibition (LI) of a classically conditioned association are two paradigms that have been widely studied as animal behavioural models of psychosis. In this study we assessed the effects of withdrawal from the repeated intermittent administration of cocaine on LI of a conditioned fear response. Animals which were either preexposed (PE) to a tone conditioned stimulus (CS) or naive to the tone (i.e. non‐preexposed: NPE) subsequently experienced 10 pairings of the tone CS with footshock. Afterwards, both groups received five daily injections of cocaine (20 mg/kg, i.p.) or saline. After 3 days of withdrawal from drug treatment, animals were tested for conditioned freezing to the context of the footshock chamber, and 1 day later, for conditioned freezing to the tone CS. Cocaine‐sensitized animals exhibited markedly enhanced LI compared to saline‐treated animals, due to the fact that NPE–cocaine animals spent more time freezing during the tone CS than NPE–saline animals, whereas PE–cocaine animals showed a tendency toward reduced freezing compared to the saline groups. While these results suggest the presence of increased anxiety in cocaine‐withdrawn NPE animals, the absence of this effect in cocaine‐withdrawn PE rats indicates that cocaine withdrawal also influences the retrieval of previously learned information.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"18 1","pages":"13-23"},"PeriodicalIF":0.0,"publicationDate":"2001-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91224892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-02-01DOI: 10.1097/00008877-200102000-00006
J. Maes, J. Ben-Michael, JoM. H. Vossen
This study assessed the effects of acute amphetamine and ketamine on the performance of rats in a serial negative patterning procedure. A 5 s auditory target stimulus and a 5 s visual feature cue were each followed by food, but the target stimulus was not followed by food if preceded by the feature. There was a 5 s empty gap between feature termination and target onset in the latter, non-reinforced trials. Thus, the feature functioned as a cue signalling the non-reinforcement of the target. The interval between the feature and the target was varied in the non-reinforced trials following pretreatment with subcutaneous saline, d -amphetamine (0.5 mg/kg) or ketamine (5 mg/kg). The main behaviour measured was visits to the place of food delivery during target presentation. Under saline, the response frequency during the target was lowest when the interval between the feature and the target exactly matched the interval used during training. Either shortening or lengthening the interval enhanced responding. Neither d -amphetamine nor ketamine disturbed this temporal pattern, although d -amphetamine and ketamine non-specifically increased and decreased response frequencies, respectively, in all the trial types. The results are discussed in the framework of the amphetamine and ketamine models of schizophrenia.
{"title":"Effects of acute d -amphetamine and ketamine on the performance of rats in a serial negative patterning procedure","authors":"J. Maes, J. Ben-Michael, JoM. H. Vossen","doi":"10.1097/00008877-200102000-00006","DOIUrl":"https://doi.org/10.1097/00008877-200102000-00006","url":null,"abstract":"This study assessed the effects of acute amphetamine and ketamine on the performance of rats in a serial negative patterning procedure. A 5 s auditory target stimulus and a 5 s visual feature cue were each followed by food, but the target stimulus was not followed by food if preceded by the feature. There was a 5 s empty gap between feature termination and target onset in the latter, non-reinforced trials. Thus, the feature functioned as a cue signalling the non-reinforcement of the target. The interval between the feature and the target was varied in the non-reinforced trials following pretreatment with subcutaneous saline, d -amphetamine (0.5 mg/kg) or ketamine (5 mg/kg). The main behaviour measured was visits to the place of food delivery during target presentation. Under saline, the response frequency during the target was lowest when the interval between the feature and the target exactly matched the interval used during training. Either shortening or lengthening the interval enhanced responding. Neither d -amphetamine nor ketamine disturbed this temporal pattern, although d -amphetamine and ketamine non-specifically increased and decreased response frequencies, respectively, in all the trial types. The results are discussed in the framework of the amphetamine and ketamine models of schizophrenia.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"93 1","pages":"53-60"},"PeriodicalIF":0.0,"publicationDate":"2001-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74956870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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