Testing Antipsychotic Drug Effects with Operant Behavioral Techniques

Lehr, E.

doi:10.1007/978-3-642-67538-6_5

Cited by 10 publications

(4 citation statements)

References 22 publications

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“…Since the mesolimbic DA system is thought to form an important component of the reward systems of the brain, it has been suggested that the increase in mesolimbic DA secretion evoked by nicotine may account for the rewarding properties of the drug which mediate it's self-administration by both experimental animals and humans (Wise & Bozarth, 1987). However, drugs which block central DA receptors have been shown to cause a preferential disruption of avoidance performance (Lehr, 1980). In addition, a recent study in my laboratory has shown that d-amphetamine, like nicotine, facilitates the acquisition of a stressful shock avoidance task and that if the drug is given during training, its withdrawal results a disruption of avoidance behaviour very similar to that seen following the withdrawal of nicotine (Balfour, 1990a).…”

Section: Introductionmentioning

confidence: 99%

The influence of stress on psychopharmacological responses to nicotine

Balfour

1991

British Journal of Addiction

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This essay considers the mechanisms which may mediate the apparent anxiolytic properties of nicotine and which are thought to be responsible for the 'calming' effect of tobacco smoke experienced by many smokers. It summarizes the evidence that, in many tests for anxiolytic activity, the effects of nicotine do not resemble those of established anxiolytic drugs such as diazepam and concludes that it is likely that neural systems other than those which mediate the responses to the benzodiazepines are responsible for the putative anxiolytic properties of nicotine. Circumstantial evidence which suggests that the increase in mesolimbic dopamine secretion evoked by nicotine may not only be rewarding per se but may also contribute to the ability of the drug to alleviate the effects of stress is presented. The essay also summarizes results which suggest that chronic nicotine evokes changes in the mesolimbic dopamine system which resemble those seen in animals treated chronically with antidepressant drugs and proposes that the mechanisms which mediate the ability of antidepressant drugs to alleviate the effects of stress may also mediate the apparent anxiolytic properties of nicotine. The possible consequences of this hypothesis for future research are considered.

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Section: Introductionmentioning

confidence: 99%

The influence of stress on psychopharmacological responses to nicotine

Balfour

1991

British Journal of Addiction

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“…Nevertheless, reports from a number of laboratories suggest that the locomotor stimulant properties of both drugs are related to their ability to stimulate preferentially the mesolimbic DA system of the brain (Kelly et a1 1975;Di Chiara & Imperato 1988;Clarke et a1 1988). Studies in other laboratories have also shown that neuroleptics disrupt avoidance performance and that the free avoidance schedule used in this study is particularly sensitive to this effect of the drugs (Lehr 1980). Thus, the data appear consistent with the hypothesis that the rats may have become dependent upon the enhanced levels of DA secretion evoked by administration of the stimulant drugs during training and that the locomotor stimulant properties of these agents by themselves may not be responsible for their effects on shock avoidance behaviour in this paradigm.…”

Section: Discussionmentioning

confidence: 66%

A Comparison of the Effects of Nicotine and (+)-Amphetamine on Rat Behaviour in an Unsignalled Sidman Avoidance Schedule

Balfour

1990

Journal of Pharmacy and Pharmacology

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In agreement with the results of previous studies, the withdrawal of nicotine from rats trained on an unsignalled Sidman avoidance schedule under the influence of the drug (0.4 mg kg-1 given subcutaneously 3 min before each training session) was associated with a reduction in lever-pressing responses (P less than 0.05) and an increase in the number of shocks received (P less than 0.01). The number of shocks received by the withdrawn rats was also greater (P less than 0.05) than the number of shocks received by rats trained and tested with saline, whereas the number of lever-pressing responses recorded for saline-treated rats was not influenced significantly by the drug used during training. The subcutaneous administration of (+)-amphetamine (0.5 mg kg-1 30 min before the test session) stimulated lever-pressing in rats trained with saline or nicotine and abolished the increase in the number of shocks received by the nicotine-withdrawn rats, but had no significant effect on the number of shocks received by rats trained with saline. The number of shocks received by the rats trained on the schedule with (+)-amphetamine but tested after an injection of saline was also greater (P less than 0.05) than the number of shocks received by rats trained and tested with saline. It is concluded that the disruption in shock avoidance performance observed for the nicotine- and (+)-amphetamine-withdrawn rats may reflect the development of dependence upon the stimulant properties of these drugs.

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“…This finding probably reflccts increased plasma and tissue concentrations of the drug following this route of administration, because the ABSo following intraperitoneal administration was also lower. Reduction of avoidance responding, accompanied by an increase in escape responding, is a classical behavioral feature of most currently marketed antipsychotic agents [Fielding and Lal, 1978;Lehr, 1980;Worms et al, 19831. Given that Wy 47,384 shares this profile in conditioned avoidance tests, one would predict clinical antipsychotic efficacy for this compound.…”

Section: Discussionmentioning

confidence: 99%

“…2). A reduction in avoidance responding accompanied by a concomitant increase in escape responses in conditioned avoidance procedures is a classical indication of preclinical antipsychotic activity [Fielding and Lal, 1978;Lehr, 1980;Worms et al, 1Y831. In nondrug sessions, the numbers of "escape responses' ' and "no-response-during-trial responses" were low (0-3 responsesisession). After Wy 47,384 treatment, these responses increased to approximately 20 responses per session, which caused the percent-of-control scores to be rather large.…”

Section: Shelf-jump Conditioned Avoidancementioning

confidence: 99%

Behavioral pharmacology of the gamma carboline Wy 47,384: A potential antipsychotic agent

Moyer¹,

Abou‐Gharbia²,

Muth³

1988

Drug Development Research

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Wy 47,384 was examined in an extensive series of in vivo preclinical behavioral tests to determine its possible efficacy and side effect liability as a novel antipsychotic agent. Wy 47,384 was found to suppress avoidance responding following both i.p. and p.o. administration at doses that did not generally impair escape performance. Wy 47,384 also was found to be considerably more potent in antagonizing climbing behavior than stereotyped behavior produced by apomorphine. However, this compound demonstrated some cataleptogenic potential in catalepsy and global behavioral assessment tests. Wy 47,384 also produced limited sedation in motor activity, conflict, and rotorod ataxia tests, but the compound did not interact with ethanol. Wy 47,384 did not demonstrate preclinical anxiolytic activity in conflict behavior tests, and it did not show antidepressant effects in tests designed to assess beta‐adrenergic sensitivity. These studies show that Wy 47,384 is a specific putative antipsychotic agent with limited extrapyramidal and sedative side effect potential.

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Testing Antipsychotic Drug Effects with Operant Behavioral Techniques

Cited by 10 publications

References 22 publications

The influence of stress on psychopharmacological responses to nicotine

The influence of stress on psychopharmacological responses to nicotine

A Comparison of the Effects of Nicotine and (+)-Amphetamine on Rat Behaviour in an Unsignalled Sidman Avoidance Schedule

Behavioral pharmacology of the gamma carboline Wy 47,384: A potential antipsychotic agent

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