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Science 17 June 1983:
Vol. 220. no. 4603, pp. 1304 - 1306
DOI: 10.1126/science.6857251
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Articles

Science, Vol 220, Issue 4603, 1304-1306
Copyright © 1983 by American Association for the Advancement of Science

articles

Pimozide blocks establishment but not expression of amphetamine-produced environment-specific conditioning

RJ Beninger and BL Hahn

Animals with a history of receiving daily injections of +-amphetamine in a specific environment showed a placebo effect (enhanced activity) when injected with saline and placed there; control animals with similar but dissociated drug histories and experience with the test chamber failed to show the effect. The dopamine receptor blocker pimozide antagonized the establishment of conditioning. However, the same dose of pimozide, when given to previously conditioned animals on the placebo test day, failed to antagonize the expression of conditioned activity. Thus, during conditioning dopaminergic neurons mediated a change that subsequently influenced behavior even when dopaminergic systems were blocked. Although schizophrenia may be related to hyperfunctioning of dopamine, neuroleptic drugs, which block dopamine receptors on their first administration, do not have therapeutic effects for a number of days. The results of the pimozide experiments may resolve this paradox.


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