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Induction by Antipsychotics of âWin-Shiftâ in the Drug Discrimination Paradigm
In a two-lever, food-rewarded drug discrimination paradigm, behavior seems to be governed by a win-stay/lose-shift rule; rats continue to press the lever that yields food, and, when not rewarded, they shift responding to the alternative lever. Here, we report on the effects that antipsychotics and f...
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Published in: | The Journal of pharmacology and experimental therapeutics 2007-07, Vol.322 (1), p.288 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | In a two-lever, food-rewarded drug discrimination paradigm, behavior seems to be governed by a win-stay/lose-shift rule; rats
continue to press the lever that yields food, and, when not rewarded, they shift responding to the alternative lever. Here,
we report on the effects that antipsychotics and further neuropharmacological agents exert in those conditions. At higher
doses, antipsychotics disrupt most or all behavioral parameters in this paradigm. However, at lower doses, rats may select
the appropriate lever with normal latency and accuracy, obtain a first food pellet (i.e., âwinâ), and then, remarkably, shift
responding to the alternative lever (âwin-shiftâ). This suggests that antipsychotics can block the effects of reward selectively,
i.e., at doses where the initial, secondarily reinforced behavior including the initiation of lever pressing, remains intact.
Indeed, saline-treated rats that are given no reward (i.e., âloseâ) after having selected a lever, also press the alternative
lever (âlose-shiftâ). The induction of selective win-shift is specific to antipsychotics, but it varies greatly among them.
Perhaps relating to its alleged âincisiveâ action on delirium and hallucinations, and, surprisingly, in view of its extrapyramidal
actions, acutely administered haloperidol (0.04â0.08 mg/kg) demonstrates win-shift to an exceptional extent, shared only with
the newly proposed agent (3-cyclopent-1-enyl-benzyl)-[2-(2,2-dimethyl-2,3-dihydro-benzofuran-7-yloxy)-ethyl]-amine fumarate
(F 15063; 0.31â0.63 mg/kg); the more sedative antipsychotic chlorpromazine demonstrated little selectivity. The paradigm offers
a novel tool to characterize antipsychotics with regard to presumably pathogenic motivational processes; mixed D 2 -antagonist/5-hydroxytryptamine 1A -agonist agents such as F 15063 may conceivably share the powerful antipsychotic action of haloperidol while avoiding the
sensitization that develops to extrapyramidal effects of haloperidol and consequent negative symptoms. |
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ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.107.119446 |