Pub Date : 2001-09-01DOI: 10.1097/00008877-200109000-00008
S. Wachtel, H. de Wit
Patients receiving therapy with hydrocortisone often report that this drug produces stimulant‐like effects or feelings of well‐being. However, little is known about the mood‐elevating effects of hydrocortisone after acute administration. Four healthy volunteers (two men and two women) received intravenous doses of hydrocortisone (0, 25, 50, 100 or 200 mg) on five separate sessions. Plasma levels of cortisol and adrenocorticotropic hormone (ACTH) were obtained, vital signs were monitored, and subjects completed a series of standardized subjective effects questionnaires. Despite large increases in circulating levels of cortisol, hydrocortisone did not produce any detectable stimulant‐like effect on mood or vital signs. To the contrary, hydrocortisone had a mild sedative‐like effect, decreasing ‘arousal’. These preliminary data indicate that acute increases in cortisol do not have either subjective stimulant‐like or mood‐elevating effects.
{"title":"Lack of effect of intravenous hydrocortisone on mood in humans: a preliminary study","authors":"S. Wachtel, H. de Wit","doi":"10.1097/00008877-200109000-00008","DOIUrl":"https://doi.org/10.1097/00008877-200109000-00008","url":null,"abstract":"Patients receiving therapy with hydrocortisone often report that this drug produces stimulant‐like effects or feelings of well‐being. However, little is known about the mood‐elevating effects of hydrocortisone after acute administration. Four healthy volunteers (two men and two women) received intravenous doses of hydrocortisone (0, 25, 50, 100 or 200 mg) on five separate sessions. Plasma levels of cortisol and adrenocorticotropic hormone (ACTH) were obtained, vital signs were monitored, and subjects completed a series of standardized subjective effects questionnaires. Despite large increases in circulating levels of cortisol, hydrocortisone did not produce any detectable stimulant‐like effect on mood or vital signs. To the contrary, hydrocortisone had a mild sedative‐like effect, decreasing ‘arousal’. These preliminary data indicate that acute increases in cortisol do not have either subjective stimulant‐like or mood‐elevating effects.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"1 1","pages":"373-376"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80526246","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 : 2001-09-01DOI: 10.1097/00008877-200109000-00003
K. Williams, Kane Ec, J. Woods
Opioid antagonists, such as naltrexone (NTX), reduce ethanol consumption and opioid agonists increase or decrease ethanol consumption in rats depending upon the dose. If the opioid antagonist and agonist effects on ethanol consumption are mediated by mu‐opioid receptors, then NTX doses that reduce ethanol consumption should be similar to the doses necessary to antagonize the effects of opioid agonists on ethanol consumption. The purpose of these experiments was: (1) to determine whether morphine increases ethanol consumption in rhesus monkeys as it does in rodents; (2) to determine if the mu‐receptor mediates the effects of morphine on ethanol consumption by conducting a p K B analysis using NTX; and (3) to determine if the mu‐receptor also mediates the NTX‐induced decreases in ethanol consumption by making comparisons between the NTX doses that affect ethanol consumption and the NTX doses that block the effects of morphine on ethanol consumption. Three male rhesus monkeys responded for 2% ethanol and water for 2 h/day on a fixed‐ratio 4 schedule of reinforcement. Morphine doses as low as 0.0032 mg/kg failed to increase ethanol fluid deliveries, whereas higher doses produced a dose‐related decrease in ethanol fluid deliveries. Although 0.01 mg/kg NTX alone had no effect on ethanol fluid deliveries, it reduced the suppressant effects of morphine with a mu‐receptor p K B of 8.21 (8.08–8.34). When given alone, 0.1 mg/kg NTX decreased ethanol fluid deliveries but failed to reverse the suppression caused by 1 mg/kg morphine. Therefore, monkeys may differ from rats in their response to morphine when ethanol consumption is the dependent variable. Furthermore, because the NTX dose that reduced the effects of morphine on responding for ethanol was smaller than the NTX doses that suppressed ethanol‐reinforced responding when given alone, NTX may exert these two effects through different mechanisms.
阿片类拮抗剂，如纳曲酮(NTX)，减少乙醇消耗量，阿片类激动剂增加或减少乙醇消耗量取决于剂量。如果阿片类拮抗剂和激动剂对乙醇消耗的作用是由mu -阿片受体介导的，那么减少乙醇消耗的NTX剂量应该与拮抗阿片类激动剂对乙醇消耗的作用所需的剂量相似。这些实验的目的是:(1)确定吗啡是否会像在啮齿类动物中一样增加恒河猴的乙醇消耗量;(2)利用NTX进行p - K - B分析，确定mu受体是否介导吗啡对乙醇消耗的影响;(3)通过比较影响乙醇消耗的NTX剂量和阻断吗啡对乙醇消耗影响的NTX剂量，确定mu受体是否也介导了NTX诱导的乙醇消耗减少。3只雄性恒河猴对2%乙醇和水每天2小时的固定比例强化有反应。吗啡剂量低至0.0032 mg/kg不能增加乙醇液体输送量，而更高剂量则会导致乙醇液体输送量的剂量相关减少。虽然单独使用0.01 mg/kg的NTX对乙醇液体输送没有影响，但它降低了吗啡的抑制作用，其mu受体p K B值为8.21(8.08-8.34)。单独给药时，0.1 mg/kg的NTX减少了乙醇液体的输送，但未能逆转1 mg/kg吗啡引起的抑制。因此，当乙醇消耗量为因变量时，猴子对吗啡的反应可能与大鼠不同。此外，由于单独给药时，减少吗啡对乙醇反应的剂量小于抑制乙醇增强反应的剂量，NTX可能通过不同的机制发挥这两种作用。
{"title":"Interaction of morphine and naltrexone on oral ethanol self‐administration in rhesus monkeys","authors":"K. Williams, Kane Ec, J. Woods","doi":"10.1097/00008877-200109000-00003","DOIUrl":"https://doi.org/10.1097/00008877-200109000-00003","url":null,"abstract":"Opioid antagonists, such as naltrexone (NTX), reduce ethanol consumption and opioid agonists increase or decrease ethanol consumption in rats depending upon the dose. If the opioid antagonist and agonist effects on ethanol consumption are mediated by mu‐opioid receptors, then NTX doses that reduce ethanol consumption should be similar to the doses necessary to antagonize the effects of opioid agonists on ethanol consumption. The purpose of these experiments was: (1) to determine whether morphine increases ethanol consumption in rhesus monkeys as it does in rodents; (2) to determine if the mu‐receptor mediates the effects of morphine on ethanol consumption by conducting a p K B analysis using NTX; and (3) to determine if the mu‐receptor also mediates the NTX‐induced decreases in ethanol consumption by making comparisons between the NTX doses that affect ethanol consumption and the NTX doses that block the effects of morphine on ethanol consumption. Three male rhesus monkeys responded for 2% ethanol and water for 2 h/day on a fixed‐ratio 4 schedule of reinforcement. Morphine doses as low as 0.0032 mg/kg failed to increase ethanol fluid deliveries, whereas higher doses produced a dose‐related decrease in ethanol fluid deliveries. Although 0.01 mg/kg NTX alone had no effect on ethanol fluid deliveries, it reduced the suppressant effects of morphine with a mu‐receptor p K B of 8.21 (8.08–8.34). When given alone, 0.1 mg/kg NTX decreased ethanol fluid deliveries but failed to reverse the suppression caused by 1 mg/kg morphine. Therefore, monkeys may differ from rats in their response to morphine when ethanol consumption is the dependent variable. Furthermore, because the NTX dose that reduced the effects of morphine on responding for ethanol was smaller than the NTX doses that suppressed ethanol‐reinforced responding when given alone, NTX may exert these two effects through different mechanisms.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"61 1","pages":"325-333"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79489410","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 : 2001-09-01DOI: 10.1097/00008877-200109000-00006
T. Mello e Souza, C. Rodrigues, M. M. Souza, E. Vinadé, A. Coitinho, H. Choi, I. Izquierdo
Adult male Wistar rats were bilaterally implanted with indwelling cannulae in the agranular insular cortex of the prefrontal cortex. After recovery, animals were trained in a step‐down inhibitory avoidance task (3.0‐s, 0.4‐mA footshock) and received, immediately after training, a 0.5‐μl infusion of the serotonergic type 1A (5‐HT 1A ) receptor agonist dipropylamino‐8‐hydroxy‐1,2,3,4‐tetrahydronaphthalene hydrobromide (8‐OH‐DPAT) or of the 5‐ HT 1A receptor antagonist 1‐(2‐methoxyphenyl)‐4‐[4‐(2‐phthalimido)butyl] piperazine hydrobromide (NAN‐190), or of vehicle alone (20% DMSO). Retention testing was carried out 24 h after training. 8‐OH‐DPAT (1.25 and 6.25 μg but not 0.0125 or 0.125 μg) was amnesic. NAN‐190 was not effective at 0.125 or 1.25 μg any dose but reversed amnesia when given at 1.250 μg simultaneously with both effective doses of 8‐OH‐DPAT. These results show that an overactivation of 5‐HT 1A receptors in the agranular insular cortex impairs memory consolidation of inhibitory avoidance, in rats, immediately after training. This suggests that these receptors of the insular cortex may modulate memory consolidation.
{"title":"Involvement of the serotonergic type 1A (5‐HT 1A ) receptor in the agranular insular cortex in the consolidation of memory for inhibitory avoidance in rats","authors":"T. Mello e Souza, C. Rodrigues, M. M. Souza, E. Vinadé, A. Coitinho, H. Choi, I. Izquierdo","doi":"10.1097/00008877-200109000-00006","DOIUrl":"https://doi.org/10.1097/00008877-200109000-00006","url":null,"abstract":"Adult male Wistar rats were bilaterally implanted with indwelling cannulae in the agranular insular cortex of the prefrontal cortex. After recovery, animals were trained in a step‐down inhibitory avoidance task (3.0‐s, 0.4‐mA footshock) and received, immediately after training, a 0.5‐μl infusion of the serotonergic type 1A (5‐HT 1A ) receptor agonist dipropylamino‐8‐hydroxy‐1,2,3,4‐tetrahydronaphthalene hydrobromide (8‐OH‐DPAT) or of the 5‐ HT 1A receptor antagonist 1‐(2‐methoxyphenyl)‐4‐[4‐(2‐phthalimido)butyl] piperazine hydrobromide (NAN‐190), or of vehicle alone (20% DMSO). Retention testing was carried out 24 h after training. 8‐OH‐DPAT (1.25 and 6.25 μg but not 0.0125 or 0.125 μg) was amnesic. NAN‐190 was not effective at 0.125 or 1.25 μg any dose but reversed amnesia when given at 1.250 μg simultaneously with both effective doses of 8‐OH‐DPAT. These results show that an overactivation of 5‐HT 1A receptors in the agranular insular cortex impairs memory consolidation of inhibitory avoidance, in rats, immediately after training. This suggests that these receptors of the insular cortex may modulate memory consolidation.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"14 1","pages":"349-353"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87472362","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 : 2001-09-01DOI: 10.1097/00008877-200109000-00001
A. Goudie, L. Baker, J. A. Smith, A. Prus, K. Svensson, L. Cortes-Burgos, E. Wong, S. Haadsma-Svensson
Dopamine D 3 receptors have been implicated in the aetiology of schizophrenia and the actions of antipsychotic drugs. The initial studies reported here assessed the involvement of such receptors in the in vivo actions of the atypical antipsychotic clozapine and the putative D 3 ‐preferring antagonist PNU‐99194A in drug discrimination assays. Rats trained to discriminate clozapine consistently generalized to PNU‐99194A in two separate studies. However, four other putative D 3 ‐preferring antagonists (PD 152255, (+)‐S14297, nafadotride and (+)‐AJ 76) did not induce generalization to clozapine. In rats trained to discriminate PNU‐99194A, which has been suggested to induce a stimulus mediated specifically by D 3 antagonism, the D 3 ‐preferring antagonist (+)‐UH 232 and clozapine both induced full generalization. However, the PNU‐99194A‐trained animals also generalized fully to the muscarinic antagonists scopolamine and trihexyphenidyl. A possible explanation for the symmetrical generalization observed between clozapine and PNU‐99194A is that these drugs have common muscarinic antagonist actions, since muscarinic antagonists have been reported to substitute for clozapine in numerous prior studies. However, in vitro receptor binding studies with M 1 −M 5 receptors indicated that (with the possible exception of the M 4 receptor), no muscarinic receptor subtype had high affinity for both clozapine, PNU‐99194A and scopolamine. In addition, other binding studies indicated that whereas clozapine and PNU‐99194A had high affinity for the D 3 receptor, scopolamine did not. It is therefore concluded that: (1) The generalization seen between clozapine, PNU‐99194A and muscarinic antagonists may be mediated by common effects ‘downstream’ from either muscarinic or D 3 receptors; (2) D 3 antagonism does not play a critical role in the clozapine stimulus (since D 3 ‐preferring antagonists did not consistently induce generalization to clozapine); (3) although D 3 antagonism plays a role in the PNU‐91994A stimulus (since the D 3 ‐preferring antagonist (+)‐UH 232 induced full generalization, in accord with results from prior studies with other D 3 ‐preferring antagonists), the PNU‐99194A stimulus also has commonalities with that induced by muscarinic antagonists and clozapine. The in vivo differences observed between PNU‐99194A and other D 3 ‐preferring antagonists should be borne in mind when this agent is used as a tool to study D 3 receptor functioning in vivo. The similarities between the PNU‐99194A and clozapine stimuli suggest tentatively that compounds with a profile like PNU‐99194A may have antipsychotic actions similar to clozapine. Some preclinical data are suggestive of such effects of PNU‐99194A.
{"title":"Common discriminative stimulus properties in rats of muscarinic antagonists, clozapine and the D 3 preferring antagonist PNU‐99194A: an analysis of possible mechanisms","authors":"A. Goudie, L. Baker, J. A. Smith, A. Prus, K. Svensson, L. Cortes-Burgos, E. Wong, S. Haadsma-Svensson","doi":"10.1097/00008877-200109000-00001","DOIUrl":"https://doi.org/10.1097/00008877-200109000-00001","url":null,"abstract":"Dopamine D 3 receptors have been implicated in the aetiology of schizophrenia and the actions of antipsychotic drugs. The initial studies reported here assessed the involvement of such receptors in the in vivo actions of the atypical antipsychotic clozapine and the putative D 3 ‐preferring antagonist PNU‐99194A in drug discrimination assays. Rats trained to discriminate clozapine consistently generalized to PNU‐99194A in two separate studies. However, four other putative D 3 ‐preferring antagonists (PD 152255, (+)‐S14297, nafadotride and (+)‐AJ 76) did not induce generalization to clozapine. In rats trained to discriminate PNU‐99194A, which has been suggested to induce a stimulus mediated specifically by D 3 antagonism, the D 3 ‐preferring antagonist (+)‐UH 232 and clozapine both induced full generalization. However, the PNU‐99194A‐trained animals also generalized fully to the muscarinic antagonists scopolamine and trihexyphenidyl. A possible explanation for the symmetrical generalization observed between clozapine and PNU‐99194A is that these drugs have common muscarinic antagonist actions, since muscarinic antagonists have been reported to substitute for clozapine in numerous prior studies. However, in vitro receptor binding studies with M 1 −M 5 receptors indicated that (with the possible exception of the M 4 receptor), no muscarinic receptor subtype had high affinity for both clozapine, PNU‐99194A and scopolamine. In addition, other binding studies indicated that whereas clozapine and PNU‐99194A had high affinity for the D 3 receptor, scopolamine did not. It is therefore concluded that: (1) The generalization seen between clozapine, PNU‐99194A and muscarinic antagonists may be mediated by common effects ‘downstream’ from either muscarinic or D 3 receptors; (2) D 3 antagonism does not play a critical role in the clozapine stimulus (since D 3 ‐preferring antagonists did not consistently induce generalization to clozapine); (3) although D 3 antagonism plays a role in the PNU‐91994A stimulus (since the D 3 ‐preferring antagonist (+)‐UH 232 induced full generalization, in accord with results from prior studies with other D 3 ‐preferring antagonists), the PNU‐99194A stimulus also has commonalities with that induced by muscarinic antagonists and clozapine. The in vivo differences observed between PNU‐99194A and other D 3 ‐preferring antagonists should be borne in mind when this agent is used as a tool to study D 3 receptor functioning in vivo. The similarities between the PNU‐99194A and clozapine stimuli suggest tentatively that compounds with a profile like PNU‐99194A may have antipsychotic actions similar to clozapine. Some preclinical data are suggestive of such effects of PNU‐99194A.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"1 1","pages":"303-315"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82308523","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 : 2001-09-01DOI: 10.1097/00008877-200109000-00002
M. Gaiardi, C. Gubellini, R. Dall'olio, O. Gandolfi, M. Bartoletti
The present study assessed the interactions between N ‐methyl‐ d ‐aspartate (NMDA) agonists or antagonists and the discriminative stimulus effects of amphetamine. Adult male Sprague–Dawley rats were trained to discriminate 0.5 mg/kg (i.p.) of amphetamine from saline under a two‐lever fixed‐ratio schedule of food reinforcement. During test sessions, i.p. injections of the glycine site agonist d ‐cycloserine, the ion‐channel blocker dizocilpine and the competitive antagonist CGP 43487 were coadministered with i.p. saline or with a full range of doses of amphetamine. d ‐Cycloserine did not substitute for amphetamine and attenuated the cueing effects of the drug. Both dizocilpine and CGP 43487 engendered intermediate levels of amphetamine‐appropriate responses and potentiated the stimulus properties of amphetamine; however, the effects of CGP 43487 were very small and not dose‐dependent. In an ancillary experiment, the training dose of amphetamine was reduced to 0.25 mg/kg; under these conditions dizocilpine, but not CGP 43487, produced full substitution for the discriminative stimulus effects of amphetamine. These results show that drugs affecting NMDA receptor‐based neurotransmission can modulate the discriminative stimulus effects of amphetamine.
{"title":"Effects of N ‐methyl‐ d ‐aspartate agonists and antagonists in rats discriminating amphetamine","authors":"M. Gaiardi, C. Gubellini, R. Dall'olio, O. Gandolfi, M. Bartoletti","doi":"10.1097/00008877-200109000-00002","DOIUrl":"https://doi.org/10.1097/00008877-200109000-00002","url":null,"abstract":"The present study assessed the interactions between N ‐methyl‐ d ‐aspartate (NMDA) agonists or antagonists and the discriminative stimulus effects of amphetamine. Adult male Sprague–Dawley rats were trained to discriminate 0.5 mg/kg (i.p.) of amphetamine from saline under a two‐lever fixed‐ratio schedule of food reinforcement. During test sessions, i.p. injections of the glycine site agonist d ‐cycloserine, the ion‐channel blocker dizocilpine and the competitive antagonist CGP 43487 were coadministered with i.p. saline or with a full range of doses of amphetamine. d ‐Cycloserine did not substitute for amphetamine and attenuated the cueing effects of the drug. Both dizocilpine and CGP 43487 engendered intermediate levels of amphetamine‐appropriate responses and potentiated the stimulus properties of amphetamine; however, the effects of CGP 43487 were very small and not dose‐dependent. In an ancillary experiment, the training dose of amphetamine was reduced to 0.25 mg/kg; under these conditions dizocilpine, but not CGP 43487, produced full substitution for the discriminative stimulus effects of amphetamine. These results show that drugs affecting NMDA receptor‐based neurotransmission can modulate the discriminative stimulus effects of amphetamine.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"57 1","pages":"317-324"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78119485","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 : 2001-09-01DOI: 10.1097/00008877-200109000-00005
L. Giordano, W. Bickel, T. Shahan, G. Badger
Progressive‐ratio (PR) schedules have been used widely to examine the relationship between drug consumption and drug price (i.e. demand curves) in the study of the behavioral economics of drug abuse. Sequential effects produced by the increasing response requirements of progressive‐ratio schedules might influence the shape of demand curves for drug reinforcers. This study compared progressive ratio schedule and random sequences of ratio requirements, each incremented across sessions in a within‐subject design, to determine if they produced similar behavioral economic and traditional measures of reinforcer efficacy. Self‐administration of standardized cigarette puffs (70 cc each) was studied with eight smokers. Puffs were available at nine ratio requirements (e.g. 3, 100, 300, 600, 1500, 3000, 6000, 12 000, 24 000 responses/three puffs), presented in ascending (progressive‐ratio schedule) or random sequence across daily sessions. The parameter estimates obtained on measures of reinforcing efficacy (e.g. breakpoint, peak response rates, elasticity of demand) were similar for both methods of incrementing prices. We found no evidence that PR and random sequences of fixed‐ratio (FR) schedules, incremented across daily sessions, resulted in different demand curves.
{"title":"Behavioral economics of human drug self‐administration: progressive ratio versus random sequences of response requirements","authors":"L. Giordano, W. Bickel, T. Shahan, G. Badger","doi":"10.1097/00008877-200109000-00005","DOIUrl":"https://doi.org/10.1097/00008877-200109000-00005","url":null,"abstract":"Progressive‐ratio (PR) schedules have been used widely to examine the relationship between drug consumption and drug price (i.e. demand curves) in the study of the behavioral economics of drug abuse. Sequential effects produced by the increasing response requirements of progressive‐ratio schedules might influence the shape of demand curves for drug reinforcers. This study compared progressive ratio schedule and random sequences of ratio requirements, each incremented across sessions in a within‐subject design, to determine if they produced similar behavioral economic and traditional measures of reinforcer efficacy. Self‐administration of standardized cigarette puffs (70 cc each) was studied with eight smokers. Puffs were available at nine ratio requirements (e.g. 3, 100, 300, 600, 1500, 3000, 6000, 12 000, 24 000 responses/three puffs), presented in ascending (progressive‐ratio schedule) or random sequence across daily sessions. The parameter estimates obtained on measures of reinforcing efficacy (e.g. breakpoint, peak response rates, elasticity of demand) were similar for both methods of incrementing prices. We found no evidence that PR and random sequences of fixed‐ratio (FR) schedules, incremented across daily sessions, resulted in different demand curves.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"49 1","pages":"343-347"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76222120","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 : 2001-09-01DOI: 10.1097/00008877-200109000-00007
L. Kestler, E. Walker, E. Vega
Controversy surrounds the question of whether there are dopamine (DA) receptor abnormalities in the brains of schizophrenia patients; in particular, whether DA receptors of the D 2 family are elevated in density. Methodological factors and sample characteristics have been postulated to account for differences in study outcome, but there has been no systematic analysis of the contribution of these factors to study effect sizes. This meta‐analysis of the research findings sought to determine the influence of methodologic factors and sample characteristics on the magnitude of diagnostic group differences in DA D 2 density (B max ) and affinity (K d ). The analysis suggests at least moderate effects, such that schizophrenia patients show an elevation in both values when compared to controls. These effects are amplified in medicated patients, but not solely attributable to antipsychotics. The group differences in DA D 2 receptor density and affinity increase with age among nonmedicated patients. The use of a butyrophenone ligand also yields larger effects. It is concluded that a subgroup of schizophrenia patients manifests increased DA D 2 receptor density and decreased receptor affinity. In the absence of medication, these changes may become more pronounced with age. Differences in study outcome are also partially due to methodologic factors, including the ligand.
{"title":"Dopamine receptors in the brains of schizophrenia patients: a meta‐analysis of the findings","authors":"L. Kestler, E. Walker, E. Vega","doi":"10.1097/00008877-200109000-00007","DOIUrl":"https://doi.org/10.1097/00008877-200109000-00007","url":null,"abstract":"Controversy surrounds the question of whether there are dopamine (DA) receptor abnormalities in the brains of schizophrenia patients; in particular, whether DA receptors of the D 2 family are elevated in density. Methodological factors and sample characteristics have been postulated to account for differences in study outcome, but there has been no systematic analysis of the contribution of these factors to study effect sizes. This meta‐analysis of the research findings sought to determine the influence of methodologic factors and sample characteristics on the magnitude of diagnostic group differences in DA D 2 density (B max ) and affinity (K d ). The analysis suggests at least moderate effects, such that schizophrenia patients show an elevation in both values when compared to controls. These effects are amplified in medicated patients, but not solely attributable to antipsychotics. The group differences in DA D 2 receptor density and affinity increase with age among nonmedicated patients. The use of a butyrophenone ligand also yields larger effects. It is concluded that a subgroup of schizophrenia patients manifests increased DA D 2 receptor density and decreased receptor affinity. In the absence of medication, these changes may become more pronounced with age. Differences in study outcome are also partially due to methodologic factors, including the ligand.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"45 1","pages":"355-371"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88550276","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 : 2001-09-01DOI: 10.1097/00008877-200109000-00004
A. Erp, Norihide Tachi, K. Miczek
We explored the effects of short, intermediate, and continuous social stress on daily ethanol and water intake in rats. The study was designed to: (1) detect increases in intake during hours when animals were not stressed; and (2) detect shifts in preference from solutions with high to low alcohol content. Male Long–Evans rats acquired ethanol self‐administration using a sucrose‐fading procedure, which was followed by continuous access to 10% and 3% ethanol solutions and water. After intake stabilized, rats were exposed to three periods of five consecutive days of social stress, with 8–10 days without stress in between. Short social stress consisted of being attacked and defeated by an aggressive opponent, followed by 30 min exposure to threats by the aggressive male while in a protective cage. Intermediate and continuous social stress consisted of a 6 h or 24 h ‘threat of attack’ exposure, respectively. All stress exposures reduced daily intake of 10% ethanol, did not cause changes in intake of 3% ethanol, and caused increases in water intake. No compensatory ethanol consumption was observed on stress days or after stress exposure was discontinued. These results are at variance with the hypothesis for increased alcohol consumption during or following social stress episodes.
{"title":"Short or continuous social stress: suppression of continuously available ethanol intake in subordinate rats","authors":"A. Erp, Norihide Tachi, K. Miczek","doi":"10.1097/00008877-200109000-00004","DOIUrl":"https://doi.org/10.1097/00008877-200109000-00004","url":null,"abstract":"We explored the effects of short, intermediate, and continuous social stress on daily ethanol and water intake in rats. The study was designed to: (1) detect increases in intake during hours when animals were not stressed; and (2) detect shifts in preference from solutions with high to low alcohol content. Male Long–Evans rats acquired ethanol self‐administration using a sucrose‐fading procedure, which was followed by continuous access to 10% and 3% ethanol solutions and water. After intake stabilized, rats were exposed to three periods of five consecutive days of social stress, with 8–10 days without stress in between. Short social stress consisted of being attacked and defeated by an aggressive opponent, followed by 30 min exposure to threats by the aggressive male while in a protective cage. Intermediate and continuous social stress consisted of a 6 h or 24 h ‘threat of attack’ exposure, respectively. All stress exposures reduced daily intake of 10% ethanol, did not cause changes in intake of 3% ethanol, and caused increases in water intake. No compensatory ethanol consumption was observed on stress days or after stress exposure was discontinued. These results are at variance with the hypothesis for increased alcohol consumption during or following social stress episodes.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"15 1","pages":"335-342"},"PeriodicalIF":0.0,"publicationDate":"2001-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82035092","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 : 2001-07-01DOI: 10.1097/00008877-200107000-00002
S. Collins, R. Gerdes, C. D'Addario, S. Izenwasser
To better understand the influence of κ‐opioid agonists on the effects of cocaine, rats were treated with daily injections of the selective κ‐opioid agonists U‐69593 or bremazocine. In combination with 10 mg/kg cocaine, both compounds, at a dose of 0.32 mg/kg, greatly diminished locomotor activity, and these effects were maintained over a period of 5 days. In addition, the response to a challenge injection of 10 mg/kg cocaine several days after the end of κ‐opioid agonist treatment with or without cocaine was markedly reduced. When naltrexone was given in combination with U‐69593, it blocked the reduction in cocaine‐induced locomotor activity after U‐69593 treatment alone. However, a single injection of either κ‐opioid agonist alone had no effect on cocaine‐induced locomotion several days later (i.e. no long‐term effects), suggesting that multiple injections of the κ‐opioid agonist are needed to reduce the locomotor activating effects of cocaine other than acutely. In addition, treatment with the κ‐opioid agonist U‐69593 (0.32 mg/kg) over a 5‐day period decreased dopamine transporter densities in the caudate putamen, and this was also blocked by co‐administration of naltrexone.
{"title":"Kappa opioid agonists alter dopamine markers and cocaine‐stimulated locomotor activity","authors":"S. Collins, R. Gerdes, C. D'Addario, S. Izenwasser","doi":"10.1097/00008877-200107000-00002","DOIUrl":"https://doi.org/10.1097/00008877-200107000-00002","url":null,"abstract":"To better understand the influence of κ‐opioid agonists on the effects of cocaine, rats were treated with daily injections of the selective κ‐opioid agonists U‐69593 or bremazocine. In combination with 10 mg/kg cocaine, both compounds, at a dose of 0.32 mg/kg, greatly diminished locomotor activity, and these effects were maintained over a period of 5 days. In addition, the response to a challenge injection of 10 mg/kg cocaine several days after the end of κ‐opioid agonist treatment with or without cocaine was markedly reduced. When naltrexone was given in combination with U‐69593, it blocked the reduction in cocaine‐induced locomotor activity after U‐69593 treatment alone. However, a single injection of either κ‐opioid agonist alone had no effect on cocaine‐induced locomotion several days later (i.e. no long‐term effects), suggesting that multiple injections of the κ‐opioid agonist are needed to reduce the locomotor activating effects of cocaine other than acutely. In addition, treatment with the κ‐opioid agonist U‐69593 (0.32 mg/kg) over a 5‐day period decreased dopamine transporter densities in the caudate putamen, and this was also blocked by co‐administration of naltrexone.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"54 1","pages":"237-245"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83492609","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 : 2001-07-01DOI: 10.1097/00008877-200107000-00001
Andrew C. Barrett, D. Morgan, Sari E Izenwasser, M. Picker
Partial opioid agonists can produce their actions at opioid as well as some non‐opioid sites. Although the receptor systems underlying these non‐opioid effects are not completely clear, recent studies indicate the possible involvement of activity at the dopamine uptake site. One purpose of the present investigation was to examine the ability of selected partial opioid agonists (dezocine, meperidine and [+]‐propoxyphene) with non‐opioid actions to produce cocaine‐like stimulus effects. Because non‐opioid effects can be apparent under conditions in which opioid‐mediated effects are blocked or at doses that markedly decrease responding, these opioids were also examined in combination with the opioid antagonist naltrexone. A second purpose was to determine the ability of these opioids to inhibit [ 3 H]dopamine uptake in rat caudate putamen. Cocaine and the direct‐acting dopamine agonist (−)‐quinpirole, but not (+)‐propoxyphene, butorphanol, morphine, U50,488 and pentobarbital, substituted completely for the cocaine stimulus. Dezocine substituted for the cocaine stimulus in the majority of the rats tested only when administered in combination with naltrexone. Meperidine also substituted for the cocaine stimulus in the majority of the rats tested, although this pattern of substitution was not consistently altered by naltrexone. Dezocine and meperidine inhibited [ 3 H]dopamine uptake in a manner consistent with that produced by cocaine. The results suggest that dezocine and meperidine can produce cocaine‐like stimulus effects and that these effects are likely mediated by activity at the dopamine uptake site.
{"title":"Cocaine‐like discriminative stimulus effects and [ 3 H]dopamine uptake inhibition produced by selected partial opioid agonists","authors":"Andrew C. Barrett, D. Morgan, Sari E Izenwasser, M. Picker","doi":"10.1097/00008877-200107000-00001","DOIUrl":"https://doi.org/10.1097/00008877-200107000-00001","url":null,"abstract":"Partial opioid agonists can produce their actions at opioid as well as some non‐opioid sites. Although the receptor systems underlying these non‐opioid effects are not completely clear, recent studies indicate the possible involvement of activity at the dopamine uptake site. One purpose of the present investigation was to examine the ability of selected partial opioid agonists (dezocine, meperidine and [+]‐propoxyphene) with non‐opioid actions to produce cocaine‐like stimulus effects. Because non‐opioid effects can be apparent under conditions in which opioid‐mediated effects are blocked or at doses that markedly decrease responding, these opioids were also examined in combination with the opioid antagonist naltrexone. A second purpose was to determine the ability of these opioids to inhibit [ 3 H]dopamine uptake in rat caudate putamen. Cocaine and the direct‐acting dopamine agonist (−)‐quinpirole, but not (+)‐propoxyphene, butorphanol, morphine, U50,488 and pentobarbital, substituted completely for the cocaine stimulus. Dezocine substituted for the cocaine stimulus in the majority of the rats tested only when administered in combination with naltrexone. Meperidine also substituted for the cocaine stimulus in the majority of the rats tested, although this pattern of substitution was not consistently altered by naltrexone. Dezocine and meperidine inhibited [ 3 H]dopamine uptake in a manner consistent with that produced by cocaine. The results suggest that dezocine and meperidine can produce cocaine‐like stimulus effects and that these effects are likely mediated by activity at the dopamine uptake site.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"19 1","pages":"225-235"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91265044","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：