Behavioral Pharmacology最新文献

{"title":"Lack of sex-related differences in the prevention by baclofen of the morphine withdrawal syndrome in mice","authors":"S. Diaz, A. Kemmling, M. Rubio, G. Balerio","doi":"10.1097/00008877-200102000-00009","DOIUrl":"https://doi.org/10.1097/00008877-200102000-00009","url":null,"abstract":"In previous studies we have demonstrated a possible interaction between the GABAergic and opioid systems involved in the antinociceptive effect of the GABA B agonist, baclofen (BAC). On the other hand, sex differences have been observed for the antinociceptive effect of morphine (MOR). In the present study, we analyzed sex-related differences in the MOR abstinence syndrome and its prevention with BAC. Prepubertal male and female Swiss–Webster albino mice (27–33 g) were rendered dependent by intraperitoneal (i.p.) injection of MOR (2, 4 and 8 mg/kg), twice daily for 9 days. On the tenth day the dependent animals were divided into two groups: one received naloxone (NAL) (6 mg/kg, i.p.) 60 min after the last dose of MOR, to precipitate the abstinence syndrome; the other group received BAC (2 mg/kg, i.p.) followed by NAL (6 mg/kg, i.p.), injected 30 and 60 min after the last dose of MOR, respectively. Behavioral signs were recorded in the open field for 30 min. Although there were sex differences in the MOR withdrawal syndrome, we found a lack of sex differences in the prevention of the MOR abstinence syndrome by BAC.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"90 1","pages":"75-79"},"PeriodicalIF":0.0,"publicationDate":"2001-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76315076","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}

{"title":"The D3R partial agonist, BP 897, attenuates the discriminative stimulus effects of cocaine and d -amphetamine and is not self-administered","authors":"P. Beardsley, P. Sokoloff, R. Balster, J. Schwartz","doi":"10.1097/00008877-200102000-00001","DOIUrl":"https://doi.org/10.1097/00008877-200102000-00001","url":null,"abstract":"Growing attention has been directed towards the potential involvement of the dopamine D3 receptor (D3R) in modulating effects of psychomotor stimulants. BP 897 (N-[4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl]-2-naphthylcarboxamide; aka BP 4.897 and DO897) is amongst the most selective partial agonists for the D3R receptor thus far reported. BP 897 was tested for its ability to support self-administration in rhesus monkeys (0.3–30 μg/kg) and for its ability to produce cocaine- and d -amphetamine-like discriminative stimulus effects in mice (0.01–17 mg/kg i.p.). BP 897 was not self-administered above vehicle and saline levels in any of the four monkeys tested, and produced less than 30% generalization from either the cocaine or d -amphetamine stimulus. When BP 897 was administered before administrations of cocaine or d -amphetamine, percent drug-lever selections were reduced. These results suggest that BP 897 has a profile of activity suitable for consideration as a potential treatment for cocaine dependency disorders.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"166 1","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2001-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85003690","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}

{"title":"Intravenous self-administration of heroin/cocaine combinations (speedball) using nose-poke or lever-press operant responding in mice","authors":"V. David, I. Polis, J. McDonald, L. Gold","doi":"10.1097/00008877-200102000-00003","DOIUrl":"https://doi.org/10.1097/00008877-200102000-00003","url":null,"abstract":"Acquisition and dose-related self-administration of heroin (H)/cocaine (C) combinations in C57BL/6 × SJL mice were studied in nose-poke or lever-press operant responding procedures. C57BL/6 × SJL mice readily acquired self-administration in both operant procedures with a combination of doses known to be ineffective when each drug was used alone (H:15 μg/kg and C:150 μg/kg per injection). Similar numbers of infusions were obtained under conditions of fixed-ratio (FR) 3 versus 1 for the nose-poke and lever-press responses, respectively. Dose–effect curves for heroin:cocaine combinations revealed a pattern corresponding to a leftward shift of the dose-response for intravenous cocaine self-administration. Curves were similar whether generated with 1 or 3 days of availability per dose, or including subjects that did not respond preferentially (>70% responses) to the hole or lever associated with drug delivery, along with those that did. Motor activity induced by a combination of low doses for each drug was examined (H: 0.375 mg/kg and C: 3.75 mg/kg, i.p.). Under these conditions, the combination of both drugs induced an initial cocaine-like stimulation of horizontal activity, in contrast to the tendency of heroin to decrease activity. It is concluded that heroin:cocaine combinations used in the present study had reinforcing effects in C57BL/6 × SJL mice, and produced a cocaine-like effect in the early part of drug-induced activity sessions, followed by a locomotor profile corresponding to the average of both drugs.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"8 1","pages":"25-34"},"PeriodicalIF":0.0,"publicationDate":"2001-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81215309","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}

{"title":"Reversal effect of sulpiride on rotational behaviour of rats with unilateral frontal cortex ablation: an alternative explanation for the pharmacological mechanism of its antidepressant effect","authors":"S. Kaneno, F. Fukamauchi, H. Komatsu, K. Koyama, K. Ikawa","doi":"10.1097/00008877-200102000-00008","DOIUrl":"https://doi.org/10.1097/00008877-200102000-00008","url":null,"abstract":"The antidepressant effect of sulpiride has been generally explained as the result of its preferential blocking effect on self‐inhibitory presynaptic dopamine autoreceptors at low doses. Low dose haloperidol has the same blocking effect. In rats with unilateral ablation of the frontal cortex, methamphetamine administration induced mild contralateral rotation 10 days after the operation. We examined whether low dose sulpiride and haloperidol would have the same effect on this rotational model. High dose sulpiride (100 mg/kg) or low dose haloperidol (0.05 mg/kg) prevented this methamphetamine‐induced rotation. However, low dose (15 mg/kg) sulpiride clearly reversed the direction of rotation. This reversal effect of low dose sulpiride is not explained by the preferential blocking effect on dopamine autoreceptors. The results suggest that low dose sulpiride, unlike low dose haloperidol, has a prominent blocking effect on D2 receptors in the frontal cortex. This unique effect of sulpiride may be relevant to its clinical antidepressant and anxiolytic effects at low doses.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"1 1","pages":"69-73"},"PeriodicalIF":0.0,"publicationDate":"2001-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78035911","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}

{"title":"Serotonin, noradrenaline and cognitive function: a preliminary investigation of the acute pharmacodynamic effects of a serotonin versus a serotonin and noradrenaline reuptake inhibitor","authors":"Pradeep J. Nathan, G. Sitaram, C. Stough, R. Silberstein, Avni Sali","doi":"10.1097/00008877-200011000-00011","DOIUrl":"https://doi.org/10.1097/00008877-200011000-00011","url":null,"abstract":"Comparisons of the behavioural side-effect profiles of antidepressants that inhibit either serotonin or both serotonin and noradrenaline reuptake, may reveal differences in cognitive and psychomotor functions, which may be attributed to their relative pharmacological selectivity for potentiating monoamine neurotransmission in the central nervous system. The aim of the present study was to determine the acute pharmacodynamic effects of citalopram and venlafaxine, on cognitive and psychomotor performance. Nine healthy male volunteers received a single clinical dose of citalopram, venlafaxine or amitriptyline (positive control) in a double-blind placebo-controlled design. Cognitive and psychomotor tests and a subjective measure of sedation were examined before and 1, 2 and 4 hours after drug administration. Citalopram improved psychomotor responses to sensory stimuli and sustained attention, with significant decreases in movement times of the choice reaction time test and an increase in critical flicker fusion threshold. Venlafaxine did not affect performances on any of the cognitive or psychomotor tests examined. Differences may be related to relative potencies of the compounds for monoamine reuptake inhibition.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"105 1","pages":"639-642"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74271415","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}

{"title":"A comparison of fixed and variable doses of cocaine in producing and augmenting tolerance to its effects on schedule-controlled behavior","authors":"M. Branch, M. Wilhelm, J. Pinkston","doi":"10.1097/00008877-200011000-00003","DOIUrl":"https://doi.org/10.1097/00008877-200011000-00003","url":null,"abstract":"Twelve pigeons were trained to peck a key under a fixed-ratio 20-response schedule of food presentation. Acute effects of cocaine (0.3–10.0 mg/kg), determined by administering the drug once per week, revealed dose-dependent decreases in frequency of key pecking. The pigeons were then divided into six pairs, matched with respect to acute dose–response curves. One of each pair received one of five different doses before each daily session (variable-dosing condition) and the other received a fixed dose equal to the arithmetic average of the doses experienced by its pair mate (fixed-dosing condition). Following 50 days of exposure, subjects in the variable-dosing condition were then switched to the fixed-dosing condition. Dose–response functions were then determined in both groups by substituting doses for the fixed daily dose, once per week. Rate-decreasing effects were attenuated similarly in both groups of subjects, both at the end of the variable-dosing regimen and during subsequent fixed dosing. Next, an attempt was made to increase the degree of tolerance. Specifically, pigeons in the variable-dosing condition were exposed repeatedly to a range of doses in which the largest dose was 1/8 to 1/4 log unit larger than in the original variable-dosing phase. Pigeons in the fixed-dosing group were exposed daily to the largest dose that did not eliminate key pecking by the end of the initial repeated-dosing regimen. Dose effects were determined after at least 35 days of exposure. If the dose–response function had shifted to the right, the largest dose for the variable-dosing subjects was increased by 1/8 to 1/4 log unit and the smallest dose in the sequence was eliminated, and another period of variable dosing commenced. For the fixed-dosing subjects, if the curve had shifted to the right, the fixed dose was increased by 1/8 to 1/4 log unit and the process repeated. Only very modest shifts of the dose–response function to the right were observed, and in several cases curves shifted left after exposure to larger doses. Overall the results suggest that a variable-dosing regimen holds promise as a technique for investigating the development of tolerance to the effects of cocaine, and that the magnitude of tolerance cannot be increased to any great degree by increasing the dose or doses repeatedly experienced. Additionally, it appears that experience with relatively large doses of cocaine may limit the degree to which tolerance can be developed, or decrease the magnitude of tolerance previously observed.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"18 1","pages":"555-569"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79093621","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}

{"title":"Effects of MAO inhibitors upon MPTP mice chronically treated with suprathreshold doses of l -dopa","authors":"A. Fredriksson, T. Palomo, T. Archer","doi":"10.1097/00008877-200011000-00004","DOIUrl":"https://doi.org/10.1097/00008877-200011000-00004","url":null,"abstract":"Groups of mice were administered either saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (2 × 40 mg/kg, s.c., separated by a 24-hour interval) 4–6 weeks prior to behavioural testing. At testing, all the MPTP-injected mice were repeatedly administered l -dopa (20 mg/kg, s.c., five times each week, Monday–Friday), by applying a procedure that induced a severe reduction of motor activity parameters from Day 1 to Day 25. Control (uninjected mice) received only saline and were retained only for neurochemical analysis. In each of three experiments, following the reduction of the activity-stimulating effects of l -dopa by repeated administration, a restorative effect of different monoamine oxidase (MAO) inhibitors was tested by co-administration of the test compounds (irreversible MAO-B inhibitor, reversible MAO-A inhibitors, or irreversible MAO-A/mixed MAO inhibitors) with l -dopa (20 mg/kg). In each case the MAO inhibitor was injected 60 min prior to l -dopa. l -Deprenyl (3 or 10 mg/kg, s.c.), in combination with l -dopa, reinstated locomotion and total activity, but not rearing, dose-dependently, in l -dopa-tolerant mice. The reversible MAO-A inhibitors, amiflamine and α-ethyltryptamine, in combination with l -dopa, reinstated locomotion and total activity, leaving rearing unaffected; Ro 41-1049 (3 mg/kg, s.c.) restored all three parameters of activity; locomotor activity was restored by all three doses (1, 3, and 10 mg/kg, s.c.). On the other hand, neither the irreversible MAO-A inhibitor, clorgyline, nor the mixed MAO inhibitor, phenelzine, produced any directly effective restorative increments. Neurochemical analysis confirmed the severe striatal dopamine depletion of MPTP-treated mice. These results demonstrate a synergistic and restorative action of combining certain MAO inhibitors, namely the reversible MAO-A inhibitors, with the suprathreshold dose of l -dopa in MPTP-treated, l -dopa-tolerant mice.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"19 1","pages":"571-581"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85098132","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}

{"title":"Nicotine enhances acquisition of a T‐maze visual discrimination: assessment of individual differences","authors":"J. Besheer, R. Bevins","doi":"10.1097/00008877-200011000-00008","DOIUrl":"https://doi.org/10.1097/00008877-200011000-00008","url":null,"abstract":"In the present report, rats’ performance was assessed in five tasks designed to measure behavioral response to different novel stimuli under different experimental situations. Daily nicotine treatment (0, 0.3 or 1.0 mg/kg) began after the conclusion of the behavioral tasks and continued throughout the experiment. Training of a T‐maze visual discrimination task commenced after 11 days of nicotine pretreatment. As a group, rats treated with the higher dose of nicotine (1.0 mg/kg) made fewer errors to acquire the initial T‐maze discrimination than saline‐treated controls. Activity induced by an inescapable novel environment (i.e. first behavioral screen) was positively correlated with the number of errors to acquire the initial discrimination in the T‐maze for the two nicotine‐treated groups (0.3 and 1.0 mg/kg). To examine this positive correlation further, a median split analysis was conducted on the novelty‐induced activity for each group. Nicotine, especially the high dose (1.0 mg/kg), enhanced performance in rats that were less active in the inescapable novel environment. Nicotine treatment did not affect the performance of rats that were more active in that environment. After the initial visual discrimination was acquired, the reverse discrimination was trained. Nicotine treatment did not affect performance; the number of errors to acquire the reversal for nicotine‐ and saline‐treated rats did not differ. Overall a nicotine‐induced improvement in performance is demonstrated which can be predicted by a rat's reactivity to environmental novelty.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"42 1","pages":"613-620"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79315900","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}

{"title":"Influence of training history on ethanol discrimination in rats","authors":"I. Stolerman, K.S. Olufsen","doi":"10.1097/00008877-200011000-00007","DOIUrl":"https://doi.org/10.1097/00008877-200011000-00007","url":null,"abstract":"The compound stimulus hypothesis of ethanol discrimination predicts that a history of training to discriminate drugs that mimic individual elements of the ethanol stimulus should attenuate stimulus control by other stimulus elements (associative blocking). Rats were trained initially to discriminate either chlordiazepoxide (5 mg/kg s.c., n  = 10) or dizocilpine (0.08 mg/kg i.p., n  = 10) from vehicle in two-lever procedures with food reinforcers presented on a tandem variable-interval fixed ratio schedule. Control rats received ‘sham training’ (vehicle injections only, n  = 9). All subjects were then trained to discriminate ethanol (1.5 g/kg intragastrically (i.g.)) until discrimination accuracy reached 95%. Chlordiazepoxide (1.25–10.0 mg/kg s.c.) produced more drug-appropriate responding in rats with a previous history of training to discriminate chlordiazepoxide than in either of the other two groups, but stimulus control by dizocilpine was not attenuated. Equivalent results were obtained in rats with a previous history of training to discriminate dizocilpine. Ethanol (0.375–3.0 g/kg i.g.) produced similar dose-related increases in drug-appropriate responding in all three groups. Thus, previous discrimination training modified the characteristics of ethanol discrimination in a way that may be explained by persistence of the original discriminations. The lack of evidence for associative blocking contrasts with results of previous experiments on the discrimination of compound stimuli produced by administering drug mixtures. The findings provide limited support for the hypothesis that ethanol produces a compound stimulus that includes elements of positive modulation of γ-aminobutyric acid (GABA A ) receptors and of N-methyl- d -aspartate (NMDA) antagonism.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"75 1","pages":"603-612"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76099829","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}

{"title":"d -Cycloserine, a positive modulator of NMDA receptors, inhibits serotonergic function","authors":"R. Dall'olio, O. Gandolfi, R. Gaggi","doi":"10.1097/00008877-200011000-00010","DOIUrl":"https://doi.org/10.1097/00008877-200011000-00010","url":null,"abstract":"The administration of the N-methyl- d -aspartate (NMDA)-associated glycine recognition site agonist d -cycloserine (DCS) to rats inhibited the head shakes and the forepaw treading induced by the serotonin (5HT) precursor, l -5-hydroxy-tryptophan [(−)5HTP], as well as the forepaw treading and motility elicited by the selective 5HT 1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The head shakes typically induced by the 5HT 2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), were unaffected by DCS pretreatment. The results are consistent with reduced serotonergic transmission produced by NMDA activation, as suggested by other authors. Due to the important role played in the pathogenesis of schizophrenia by glutamate deficiency/serotonin activation, the results support the view that positive modulators of NMDA receptors, activating glutamate receptors and reducing serotonergic tone, might be useful in the alleviation of psychotic symptoms. However, because of its partial agonist properties at the glycine recognition site, d -cycloserine shows some effects that might make it unsuitable for clinical use.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"301 1","pages":"631-637"},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76809789","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}