Pub Date : 2001-07-01DOI: 10.1097/00008877-200107000-00004
P. Munzar, S. Yasar, G. Redhi, Z. Justinova, S. Goldberg
Although benzodiazepines are frequently abused by humans, they usually maintain lower rates of self‐administration behavior in laboratory animals than other drugs of abuse such as psychomotor stimulants or barbiturates. In the present study, intravenous (i.v.) self‐administration of the short‐acting benzodiazepine midazolam was evaluated in squirrel monkeys. Monkeys (n = 3) initially self‐administered the short‐acting barbiturate methohexital (100#μg/kg/injection) during daily 1‐hour sessions under a fixed‐ratio 10, 60 s time‐out, schedule of i.v. drug injection. This dose of methohexital maintained high rates of responding averaging 0.9 responses per second. Midazolam was then substituted for methohexital, and midazolam dose was subsequently varied from 0.3 to 3 μg/kg/injection. Each dose of midazolam was tested for five consecutive sessions and each unit dose condition was separated by five sessions of vehicle extinction. The midazolam dose–response function was an inverted U‐shaped curve, with maximal rates of self‐administration responding averaging 1.01 responses/second at a dose of 1 μg/kg/injection (an average of 48 injections per 1‐hour session). The rates and fixed‐ratio patterns of responding maintained by self‐administration of midazolam in the present study were comparable to the rates and patterns of responding maintained in squirrel monkeys by self‐administration of other drugs of abuse, including cocaine, amphetamine, nicotine and tetrahydrocannabinol, under similar experimental conditions.
{"title":"High rates of midazolam self‐administration in squirrel monkeys","authors":"P. Munzar, S. Yasar, G. Redhi, Z. Justinova, S. Goldberg","doi":"10.1097/00008877-200107000-00004","DOIUrl":"https://doi.org/10.1097/00008877-200107000-00004","url":null,"abstract":"Although benzodiazepines are frequently abused by humans, they usually maintain lower rates of self‐administration behavior in laboratory animals than other drugs of abuse such as psychomotor stimulants or barbiturates. In the present study, intravenous (i.v.) self‐administration of the short‐acting benzodiazepine midazolam was evaluated in squirrel monkeys. Monkeys (n = 3) initially self‐administered the short‐acting barbiturate methohexital (100#μg/kg/injection) during daily 1‐hour sessions under a fixed‐ratio 10, 60 s time‐out, schedule of i.v. drug injection. This dose of methohexital maintained high rates of responding averaging 0.9 responses per second. Midazolam was then substituted for methohexital, and midazolam dose was subsequently varied from 0.3 to 3 μg/kg/injection. Each dose of midazolam was tested for five consecutive sessions and each unit dose condition was separated by five sessions of vehicle extinction. The midazolam dose–response function was an inverted U‐shaped curve, with maximal rates of self‐administration responding averaging 1.01 responses/second at a dose of 1 μg/kg/injection (an average of 48 injections per 1‐hour session). The rates and fixed‐ratio patterns of responding maintained by self‐administration of midazolam in the present study were comparable to the rates and patterns of responding maintained in squirrel monkeys by self‐administration of other drugs of abuse, including cocaine, amphetamine, nicotine and tetrahydrocannabinol, under similar experimental conditions.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"34 1","pages":"257-265"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74079628","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: 10.1097/00008877-200107000-00007
M. C. Sánchez-Amate, P. Flores, F. Sánchez-Santed
The purpose of the present study was to determine the effect of two different doses of the organophosphate insecticide O, O′–diethyl‐O ‐3,5,6‐trichloro‐2‐pyridylphosphorothionate [chlorpyrifos (CPF)], a cholinesterase (ChE) inhibitor, in the plus‐maze test of anxiety in the rat, as well as on acetylcholinesterase (AChE) activity in the brain. In a first experiment, the behavioural methodology was validated by showing the anxiolytic and anxiogenic effects of diazepam and pentylenetetrazole (PTZ), respectively. Acute exposure to CPF (166 mg/kg and 250 mg/kg, s.c.) produced significant dose‐dependent inhibition (54% and 71%, respectively) of whole‐brain AChE 48 hours after treatment. Neither dose produced signs of acute cholinergic toxicity at any time following treatment, as was verified by a functional observational battery. Both doses of CPF were injected 48 h before testing in the plus‐maze and were shown to have anxiogenic effects as demonstrated by the significant decrease in the percentage of time spent and percentage of entries into open arms. This report thus shows clear behavioural alteration as an acute effect of an organophosphate in the absence of any classic sign of cholinergic toxicity. Our results are relevant to the understanding of both the pharmacology of anxiety and the behavioural toxicology of cholinesterase inhibitors.
本研究的目的是确定两种不同剂量的有机磷杀虫剂O, O ' -二乙基- O‐3,5,6‐三氯‐2‐吡啶基硫代酸盐[毒死蜱(CPF)]，一种胆碱酯酶(ChE)抑制剂，在大鼠焦虑的正迷宫测试中，以及对大脑乙酰胆碱酯酶(AChE)活性的影响。在第一个实验中，行为方法分别通过显示安定和戊四唑(PTZ)的抗焦虑和致焦虑作用得到验证。急性暴露于CPF (166 mg/kg和250 mg/kg, s.c)在治疗后48小时对全脑AChE产生显著的剂量依赖性抑制(分别为54%和71%)。两种剂量在治疗后的任何时间都没有产生急性胆碱能毒性的迹象，这是由功能观察电池证实的。两种剂量的CPF均在阳性迷宫试验前48小时注射，结果显示CPF具有焦虑效应，其表现为花费时间百分比和进入张开双臂百分比的显著减少。因此，本报告表明，在没有任何典型胆碱能毒性迹象的情况下，行为改变是有机磷的急性效应。我们的结果与焦虑的药理学和胆碱酯酶抑制剂的行为毒理学的理解有关。
{"title":"Effects of chlorpyrifos in the plus‐maze model of anxiety","authors":"M. C. Sánchez-Amate, P. Flores, F. Sánchez-Santed","doi":"10.1097/00008877-200107000-00007","DOIUrl":"https://doi.org/10.1097/00008877-200107000-00007","url":null,"abstract":"The purpose of the present study was to determine the effect of two different doses of the organophosphate insecticide O, O′–diethyl‐O ‐3,5,6‐trichloro‐2‐pyridylphosphorothionate [chlorpyrifos (CPF)], a cholinesterase (ChE) inhibitor, in the plus‐maze test of anxiety in the rat, as well as on acetylcholinesterase (AChE) activity in the brain. In a first experiment, the behavioural methodology was validated by showing the anxiolytic and anxiogenic effects of diazepam and pentylenetetrazole (PTZ), respectively. Acute exposure to CPF (166 mg/kg and 250 mg/kg, s.c.) produced significant dose‐dependent inhibition (54% and 71%, respectively) of whole‐brain AChE 48 hours after treatment. Neither dose produced signs of acute cholinergic toxicity at any time following treatment, as was verified by a functional observational battery. Both doses of CPF were injected 48 h before testing in the plus‐maze and were shown to have anxiogenic effects as demonstrated by the significant decrease in the percentage of time spent and percentage of entries into open arms. This report thus shows clear behavioural alteration as an acute effect of an organophosphate in the absence of any classic sign of cholinergic toxicity. Our results are relevant to the understanding of both the pharmacology of anxiety and the behavioural toxicology of cholinesterase inhibitors.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"15 1","pages":"285-292"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79827648","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: 10.1097/00008877-200107000-00005
J. E. Klebaur, R. Bevins, T. Segar, M. Bardo
Previous work has shown that individual differences in locomotor activity in an inescapable novel environment can predict acquisition of amphetamine self‐administration. The current study examined whether individual differences in approach to novelty in a free choice test could also predict amphetamine self‐administration. Further, the current study examined whether individual differences in either free choice or inescapable novelty tests could predict responding for a nondrug reinforcer (sucrose) in the presence and absence of amphetamine. Male and female rats were first tested for their response to free choice novelty (playground maze and novelty‐induced place preference tests) and inescapable novelty. They were then tested for acquisition of sucrose‐reinforced responding, amphetamine‐induced changes in maintenance of sucrose‐reinforced responding, and amphetamine self‐administration. Based on the inescapable novelty test, acquisition of sucrose‐reinforced responding was more rapid in male high responders (HR) compared to low responders (LR). This effect in males did not generalize to females. None of the novelty tests predicted the ability of amphetamine to decrease sucrose‐maintained responding. However, using the inescapable novelty test, both male and female HRs self‐administered more amphetamine than LRs within the dose range tested (0.03–0.16 mg/kg/infusion). Neither the playground maze nor the novelty‐induced place preference test predicted amphetamine self‐administration. These results indicate that responses to free choice novelty and inescapable novelty predict different components of amphetamine‐induced behavior.
{"title":"Individual differences in behavioral responses to novelty and amphetamine self‐administration in male and female rats","authors":"J. E. Klebaur, R. Bevins, T. Segar, M. Bardo","doi":"10.1097/00008877-200107000-00005","DOIUrl":"https://doi.org/10.1097/00008877-200107000-00005","url":null,"abstract":"Previous work has shown that individual differences in locomotor activity in an inescapable novel environment can predict acquisition of amphetamine self‐administration. The current study examined whether individual differences in approach to novelty in a free choice test could also predict amphetamine self‐administration. Further, the current study examined whether individual differences in either free choice or inescapable novelty tests could predict responding for a nondrug reinforcer (sucrose) in the presence and absence of amphetamine. Male and female rats were first tested for their response to free choice novelty (playground maze and novelty‐induced place preference tests) and inescapable novelty. They were then tested for acquisition of sucrose‐reinforced responding, amphetamine‐induced changes in maintenance of sucrose‐reinforced responding, and amphetamine self‐administration. Based on the inescapable novelty test, acquisition of sucrose‐reinforced responding was more rapid in male high responders (HR) compared to low responders (LR). This effect in males did not generalize to females. None of the novelty tests predicted the ability of amphetamine to decrease sucrose‐maintained responding. However, using the inescapable novelty test, both male and female HRs self‐administered more amphetamine than LRs within the dose range tested (0.03–0.16 mg/kg/infusion). Neither the playground maze nor the novelty‐induced place preference test predicted amphetamine self‐administration. These results indicate that responses to free choice novelty and inescapable novelty predict different components of amphetamine‐induced behavior.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"1 1","pages":"267-275"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81488364","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: 10.1097/00008877-200107000-00006
T. Shahan, W. Bickel, G. Badger, L. Giordano
A previous report from our laboratory showed similar measures of reinforcing efficacy for nicotine‐containing and de‐nicotinized cigarettes when each cigarette type was presented alone. The present experiment further compared the reinforcing efficacy of nicotine‐containing and de‐nicotinized cigarettes by assessing the effects of alternative non‐drug reinforcement on self‐administration of both cigarette types. Eight human subjects responded on a progressive‐ratio schedule in which the number of plunger pulls required for standardized cigarette puffs increased across sessions. Responding for the two types of cigarette was examined when each was available alone and when the concurrent opportunity to earn money was available. Consumption of nicotine‐containing and de‐nicotinized cigarettes was decreased by both increases in price and by the concurrent availability of money. The two cigarettes types did not differ in their sensitivity to price or alternative non‐drug reinforcement. These results replicate our previous report of similar measures of reinforcing efficacy for the two cigarette types when each was presented alone, and extend our previous findings to a choice situation involving an alternative non‐drug reinforcer. These data suggest the importance of further examination of non‐pharmacological variables in the maintenance of drug taking and the sensitivity of drug taking to alternative non‐drug sources of reinforcement. Factors potentially contributing to the maintenance of smoking the de‐nicotinized cigarettes (i.e. conditioned reinforcement, primary reinforcement by respiratory stimulation, instructional control, demand characteristics) are also discussed.
{"title":"Sensitivity of nicotine‐containing and de‐nicotinized cigarette consumption to alternative non‐drug reinforcement: a behavioral economic analysis","authors":"T. Shahan, W. Bickel, G. Badger, L. Giordano","doi":"10.1097/00008877-200107000-00006","DOIUrl":"https://doi.org/10.1097/00008877-200107000-00006","url":null,"abstract":"A previous report from our laboratory showed similar measures of reinforcing efficacy for nicotine‐containing and de‐nicotinized cigarettes when each cigarette type was presented alone. The present experiment further compared the reinforcing efficacy of nicotine‐containing and de‐nicotinized cigarettes by assessing the effects of alternative non‐drug reinforcement on self‐administration of both cigarette types. Eight human subjects responded on a progressive‐ratio schedule in which the number of plunger pulls required for standardized cigarette puffs increased across sessions. Responding for the two types of cigarette was examined when each was available alone and when the concurrent opportunity to earn money was available. Consumption of nicotine‐containing and de‐nicotinized cigarettes was decreased by both increases in price and by the concurrent availability of money. The two cigarettes types did not differ in their sensitivity to price or alternative non‐drug reinforcement. These results replicate our previous report of similar measures of reinforcing efficacy for the two cigarette types when each was presented alone, and extend our previous findings to a choice situation involving an alternative non‐drug reinforcer. These data suggest the importance of further examination of non‐pharmacological variables in the maintenance of drug taking and the sensitivity of drug taking to alternative non‐drug sources of reinforcement. Factors potentially contributing to the maintenance of smoking the de‐nicotinized cigarettes (i.e. conditioned reinforcement, primary reinforcement by respiratory stimulation, instructional control, demand characteristics) are also discussed.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"40 1","pages":"277-284"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84823431","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: 10.1097/00008877-200107000-00008
Y. Shiigi, D. Casey
Ketamine, a noncompetitive N ‐methyl‐ d ‐aspartate (NMDA) glutamate receptor antagonist, causes a schizophrenic‐like psychosis in normal volunteers and exacerbates psychotic symptoms in patients with schizophrenia. Recent work has shown that ketamine and other NMDA antagonists affect a range of behaviors in nonhuman primates, particularly those associated with motor and mental function such as attention and perception. Several lines of study also suggest that NMDA antagonists interact with cholinergic mechanisms. The effects of benztropine, an anticholinergic agent, on ketamine‐induced behaviors were evaluated in a double‐blind randomized test design in 20 Cebus monkeys. Benztropine (0.05, 0.1 and 0.25 mg/kg, i.m.) was injected 1 hour before ketamine (2.5 and 5.0 mg/kg, i.m.) administration. Behaviors scored for 90 minutes after ketamine administration included salivation, dystonia and reactivity to external stimuli. Benztropine almost completely blocked ketamine‐induced hypersalivation, and partially ameliorated the dystonia syndrome by 50%, but did not affect ketamine‐induced decreased reactivity to external stimuli. These results suggest that cholinergic mechanisms only moderately influence ketamine‐induced central nervous system effects of motor dysfunction, and may not play a substantive role in the ketamine‐induced deficit of reactivity to external stimuli, which involves a complex interaction of mental functions such as attention and perception, as well as motor behavior.
氯胺酮是一种非竞争性N -甲基- d -天冬氨酸(NMDA)谷氨酸受体拮抗剂，在正常志愿者中引起精神分裂症样精神病，并加重精神分裂症患者的精神病症状。最近的研究表明，氯胺酮和其他NMDA拮抗剂影响非人类灵长类动物的一系列行为，特别是与运动和心理功能相关的行为，如注意力和感知。一些研究也表明NMDA拮抗剂与胆碱能机制相互作用。采用双盲随机试验设计，对20只Cebus猴进行了苯托品(一种抗胆碱能药物)对氯胺酮诱导行为的影响进行了评估。在给予氯胺酮(2.5和5.0 mg/kg, i.m.)前1小时注射苯托品(0.05、0.1和0.25 mg/kg, i.m.)。服用氯胺酮90分钟后的行为评分包括流涎、肌张力障碍和对外部刺激的反应性。苯托品几乎完全阻断了氯胺酮诱导的唾液分泌过多，并部分改善了50%的肌张力障碍综合征，但对氯胺酮诱导的对外部刺激反应性下降没有影响。这些结果表明，胆碱能机制仅适度影响氯胺酮诱导的中枢神经系统运动功能障碍，而可能在氯胺酮诱导的对外部刺激的反应性缺陷中不起实质性作用，这涉及注意、感知和运动行为等心理功能的复杂相互作用。
{"title":"Effects of benztropine on ketamine‐induced behaviors in Cebus monkeys","authors":"Y. Shiigi, D. Casey","doi":"10.1097/00008877-200107000-00008","DOIUrl":"https://doi.org/10.1097/00008877-200107000-00008","url":null,"abstract":"Ketamine, a noncompetitive N ‐methyl‐ d ‐aspartate (NMDA) glutamate receptor antagonist, causes a schizophrenic‐like psychosis in normal volunteers and exacerbates psychotic symptoms in patients with schizophrenia. Recent work has shown that ketamine and other NMDA antagonists affect a range of behaviors in nonhuman primates, particularly those associated with motor and mental function such as attention and perception. Several lines of study also suggest that NMDA antagonists interact with cholinergic mechanisms. The effects of benztropine, an anticholinergic agent, on ketamine‐induced behaviors were evaluated in a double‐blind randomized test design in 20 Cebus monkeys. Benztropine (0.05, 0.1 and 0.25 mg/kg, i.m.) was injected 1 hour before ketamine (2.5 and 5.0 mg/kg, i.m.) administration. Behaviors scored for 90 minutes after ketamine administration included salivation, dystonia and reactivity to external stimuli. Benztropine almost completely blocked ketamine‐induced hypersalivation, and partially ameliorated the dystonia syndrome by 50%, but did not affect ketamine‐induced decreased reactivity to external stimuli. These results suggest that cholinergic mechanisms only moderately influence ketamine‐induced central nervous system effects of motor dysfunction, and may not play a substantive role in the ketamine‐induced deficit of reactivity to external stimuli, which involves a complex interaction of mental functions such as attention and perception, as well as motor behavior.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"12 1","pages":"293-298"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87500032","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: 10.1097/00008877-200107000-00009
P. Pereira, P. Ardenghi, M. M. D. de Souza, H. Choi, B. Moletta, I. Izquierdo
The aim of the present work was to test the role of protein tyrosine kinases (PTKs) on both the short-term memory (STM) and long-term memory (LTM) of the inhibitory avoidance task in rats using the inhibitor of tyrosine kinase, radicicol. Rats implanted with cannulae in the CA1 area of the dorsal hippocampus received a 0.5 μl infusion of radicicol (0.5, 1, 5, 10, 20 μg/ml) or vehicle (water) at different times after training and were tested for STM (1.5 or 3 h) and LTM (24 h). Additionally, one group received radicicol 10 min prior to the test for LTM. Radicicol depressed both STM and LTM when infused before and immediately after training and had no effect on either form of memory when infused 30 or 90 min after training. Radicicol also depressed the retrieval of LTM. Our results indicate that memory formation and retrieval in the hippocampus can involve PTK activity, but the present findings should be taken merely as a possible starting point for future investigations.
{"title":"Effects of infusions of the tyrosine kinase inhibitor radicicol into the hippocampus on short- and long-term memory of the inhibitory avoidance task","authors":"P. Pereira, P. Ardenghi, M. M. D. de Souza, H. Choi, B. Moletta, I. Izquierdo","doi":"10.1097/00008877-200107000-00009","DOIUrl":"https://doi.org/10.1097/00008877-200107000-00009","url":null,"abstract":"The aim of the present work was to test the role of protein tyrosine kinases (PTKs) on both the short-term memory (STM) and long-term memory (LTM) of the inhibitory avoidance task in rats using the inhibitor of tyrosine kinase, radicicol. Rats implanted with cannulae in the CA1 area of the dorsal hippocampus received a 0.5 μl infusion of radicicol (0.5, 1, 5, 10, 20 μg/ml) or vehicle (water) at different times after training and were tested for STM (1.5 or 3 h) and LTM (24 h). Additionally, one group received radicicol 10 min prior to the test for LTM. Radicicol depressed both STM and LTM when infused before and immediately after training and had no effect on either form of memory when infused 30 or 90 min after training. Radicicol also depressed the retrieval of LTM. Our results indicate that memory formation and retrieval in the hippocampus can involve PTK activity, but the present findings should be taken merely as a possible starting point for future investigations.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"10 1","pages":"299-302"},"PeriodicalIF":0.0,"publicationDate":"2001-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86238632","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: 10.1097/00008877-200105000-00003
K. Ellis, C. Stough, L. Vitetta, K. Heinrich, P. Nathan
Hypericum perforatum L. (St. John's Wort) is a complex herb that has been used for centuries for its putative medicinal properties, and has current therapeutic relevance as a treatment of mild to moderate depression. Recently, two studies in rodents have suggested that hypericum may also have memory‐enhancing effects. It has a complex pharmacology, in that acute administration modulates numerous neurotransmitter systems that have previously been observed to either augment or impair a variety of memory processes in humans. This study aimed to examine whether acute administration of standardized hypericum extract could exert a nootropic effect in normal human subjects. The study employed a double‐blind, crossover, repeated‐measures design. Twelve healthy young subjects completed the Cognitive Drug Research (CDR) memory battery, following administration of placebo, 900 mg and 1800 mg hypericum (Blackmore's Hyperiforte). The findings suggested that hypericum does not have an acute nootropic effect in healthy humans at these doses. However, there was some evidence for an impairing effect on accuracy of numeric working memory and delayed picture recognition at the higher dose. This observed impairment could be due to a sensitivity of these specific tasks to modulation by neurotransmitters that have been noted to have memory‐impairing effects (e.g. γ‐aminobutyric acid (GABA), serotonin).
{"title":"An investigation into the acute nootropic effects of Hypericum perforatum L. (St. John's Wort) in healthy human volunteers","authors":"K. Ellis, C. Stough, L. Vitetta, K. Heinrich, P. Nathan","doi":"10.1097/00008877-200105000-00003","DOIUrl":"https://doi.org/10.1097/00008877-200105000-00003","url":null,"abstract":"Hypericum perforatum L. (St. John's Wort) is a complex herb that has been used for centuries for its putative medicinal properties, and has current therapeutic relevance as a treatment of mild to moderate depression. Recently, two studies in rodents have suggested that hypericum may also have memory‐enhancing effects. It has a complex pharmacology, in that acute administration modulates numerous neurotransmitter systems that have previously been observed to either augment or impair a variety of memory processes in humans. This study aimed to examine whether acute administration of standardized hypericum extract could exert a nootropic effect in normal human subjects. The study employed a double‐blind, crossover, repeated‐measures design. Twelve healthy young subjects completed the Cognitive Drug Research (CDR) memory battery, following administration of placebo, 900 mg and 1800 mg hypericum (Blackmore's Hyperiforte). The findings suggested that hypericum does not have an acute nootropic effect in healthy humans at these doses. However, there was some evidence for an impairing effect on accuracy of numeric working memory and delayed picture recognition at the higher dose. This observed impairment could be due to a sensitivity of these specific tasks to modulation by neurotransmitters that have been noted to have memory‐impairing effects (e.g. γ‐aminobutyric acid (GABA), serotonin).","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"294 1","pages":"173-182"},"PeriodicalIF":0.0,"publicationDate":"2001-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76305662","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: 10.1097/00008877-200105000-00007
P. Pereira, P. Ardenghi, T. Mello e Souza, J. Medina, I. Izquierdo
The cAMP/cAMP‐dependent protein kinase (PKA) signaling pathway has been implicated in synaptic plasticity changes and memory consolidation. Several cortical structures are involved in the consolidation of memory for inhibitory avoidance. The aim of the present work was to observe the effects of training in the inhibitory avoidance task on the levels of PKA activity in the entorhinal, parietal and posterior cingulate cortex (EC, PARIET and PC), and the medial precentral area (Fr2) of the rat, at different post‐training times (0, 1.5, 3 and 6 h). PKA activity, assayed using [γ‐ 32 P]ATP and kemptide, a selective substrate, increased in the EC 3 h after training, but no changes were observed in PARIET, PC and Fr2. These results suggest that the late phase of memory consolidation of inhibitory avoidance requires a functional PKA signaling pathway in the EC in a way that a ‘peak’ of PKA activity is observed.
{"title":"Training in the step‐down inhibitory avoidance task time‐dependently increases cAMP‐dependent protein kinase activity in the entorhinal cortex","authors":"P. Pereira, P. Ardenghi, T. Mello e Souza, J. Medina, I. Izquierdo","doi":"10.1097/00008877-200105000-00007","DOIUrl":"https://doi.org/10.1097/00008877-200105000-00007","url":null,"abstract":"The cAMP/cAMP‐dependent protein kinase (PKA) signaling pathway has been implicated in synaptic plasticity changes and memory consolidation. Several cortical structures are involved in the consolidation of memory for inhibitory avoidance. The aim of the present work was to observe the effects of training in the inhibitory avoidance task on the levels of PKA activity in the entorhinal, parietal and posterior cingulate cortex (EC, PARIET and PC), and the medial precentral area (Fr2) of the rat, at different post‐training times (0, 1.5, 3 and 6 h). PKA activity, assayed using [γ‐ 32 P]ATP and kemptide, a selective substrate, increased in the EC 3 h after training, but no changes were observed in PARIET, PC and Fr2. These results suggest that the late phase of memory consolidation of inhibitory avoidance requires a functional PKA signaling pathway in the EC in a way that a ‘peak’ of PKA activity is observed.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"95 1","pages":"217-220"},"PeriodicalIF":0.0,"publicationDate":"2001-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80729923","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: 10.1097/00008877-200105000-00002
M. Lanser, B. Ellenbroek, F. Zitman, D. Heeren, A. Cools
In rat studies, both lesions in the medial prefrontal cortex (mPFC) and alterations of the level of mPFC dopamine (DA) have been found to induce disturbances in behavioural flexibility, as measured with switching tasks. It is not clear whether mPFC DA is also involved in spontaneous flexibility. Therefore, the aim of the present study was to investigate the role of mPFC DA in spontaneous flexibility. As a measure for spontaneous flexibility, the diversity in spatial distribution of exploration on a large open field was used. The rats received local injections into the mPFC with a D 1 or D 2 antagonist, or the dopamimetic, amphetamine. The results showed that both DA antagonists reduced spontaneous flexibility, due to increased stimulus‐bound behaviour. Amphetamine had a similar effect to the DA antagonists. It is suggested that this is most likely due to an amphetamine‐induced increase in extracellular DA, leading to a suboptimal level of mPFC DA.
{"title":"The role of medial prefrontal cortical dopamine in spontaneous flexibility in the rat","authors":"M. Lanser, B. Ellenbroek, F. Zitman, D. Heeren, A. Cools","doi":"10.1097/00008877-200105000-00002","DOIUrl":"https://doi.org/10.1097/00008877-200105000-00002","url":null,"abstract":"In rat studies, both lesions in the medial prefrontal cortex (mPFC) and alterations of the level of mPFC dopamine (DA) have been found to induce disturbances in behavioural flexibility, as measured with switching tasks. It is not clear whether mPFC DA is also involved in spontaneous flexibility. Therefore, the aim of the present study was to investigate the role of mPFC DA in spontaneous flexibility. As a measure for spontaneous flexibility, the diversity in spatial distribution of exploration on a large open field was used. The rats received local injections into the mPFC with a D 1 or D 2 antagonist, or the dopamimetic, amphetamine. The results showed that both DA antagonists reduced spontaneous flexibility, due to increased stimulus‐bound behaviour. Amphetamine had a similar effect to the DA antagonists. It is suggested that this is most likely due to an amphetamine‐induced increase in extracellular DA, leading to a suboptimal level of mPFC DA.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"12 5 1","pages":"163-171"},"PeriodicalIF":0.0,"publicationDate":"2001-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76911309","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: 10.1097/00008877-200105000-00006
P. S. Naidu, S. K. Kulkarni
Tardive dyskinesia (TD) is a serious motor side‐effect of chronic neuroleptic therapy. Chronic treatment with neuroleptics leads to the development of oral abnormal movements in rats known as vacuous chewing movements (VCMs). Vacuous chewing movements in rats have been widely accepted as an animal model of tardive dyskinesia. Chronic blockade of D 2 inhibitory dopamine (DA) receptors localized on glutamatergic terminals in the striatum leads to the persistent enhanced release of glutamate that kills the striatal output neurons. The object of the present study was to explore the role of glutamatergic modulation on the neuroleptic‐induced VCMs. Rats were chronically (for 21 days) treated with haloperidol (1.5 mg/kg, i.p.) to produce VCMs. The neuroleptic‐induced VCMs viz., vertical jaw movements, tongue protrusions and bursts of jaw tremors, were counted during a 5 min observation period. Dizocilpine, a non‐competitive N ‐methyl‐ d ‐aspartate (NMDA) receptor antagonist, dose dependently (0.02 and 0.05 mg/kg) reduced haloperidol‐induced VCMs. Felodipine (5 and 10 mg/kg), an L‐type calcium‐channel blocker, also significantly reduced the VCM count. N‐omega‐nitro‐ l ‐arginine methyl ester ( l ‐NAME) (25 and 50 mg/kg), a nitric oxide synthase inhibitor, also reduced the VCM count in an l ‐arginine‐sensitive manner. In conclusion, the findings of the present study indicated NMDA receptor involvement in haloperidol‐induced VCMs, and also suggested the possible involvement of calcium and nitric oxide in haloperidol‐induced VCMs.
{"title":"Excitatory mechanisms in neuroleptic‐induced vacuous chewing movements (VCMs): possible involvement of calcium and nitric oxide","authors":"P. S. Naidu, S. K. Kulkarni","doi":"10.1097/00008877-200105000-00006","DOIUrl":"https://doi.org/10.1097/00008877-200105000-00006","url":null,"abstract":"Tardive dyskinesia (TD) is a serious motor side‐effect of chronic neuroleptic therapy. Chronic treatment with neuroleptics leads to the development of oral abnormal movements in rats known as vacuous chewing movements (VCMs). Vacuous chewing movements in rats have been widely accepted as an animal model of tardive dyskinesia. Chronic blockade of D 2 inhibitory dopamine (DA) receptors localized on glutamatergic terminals in the striatum leads to the persistent enhanced release of glutamate that kills the striatal output neurons. The object of the present study was to explore the role of glutamatergic modulation on the neuroleptic‐induced VCMs. Rats were chronically (for 21 days) treated with haloperidol (1.5 mg/kg, i.p.) to produce VCMs. The neuroleptic‐induced VCMs viz., vertical jaw movements, tongue protrusions and bursts of jaw tremors, were counted during a 5 min observation period. Dizocilpine, a non‐competitive N ‐methyl‐ d ‐aspartate (NMDA) receptor antagonist, dose dependently (0.02 and 0.05 mg/kg) reduced haloperidol‐induced VCMs. Felodipine (5 and 10 mg/kg), an L‐type calcium‐channel blocker, also significantly reduced the VCM count. N‐omega‐nitro‐ l ‐arginine methyl ester ( l ‐NAME) (25 and 50 mg/kg), a nitric oxide synthase inhibitor, also reduced the VCM count in an l ‐arginine‐sensitive manner. In conclusion, the findings of the present study indicated NMDA receptor involvement in haloperidol‐induced VCMs, and also suggested the possible involvement of calcium and nitric oxide in haloperidol‐induced VCMs.","PeriodicalId":8741,"journal":{"name":"Behavioral Pharmacology","volume":"14 1","pages":"209-216"},"PeriodicalIF":0.0,"publicationDate":"2001-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85228601","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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