Mixed D2/5-HT2A antagonism of amphetamine-induced facilitation of brain stimulation reward

Pharmacology, Biochemistry, and Behavior
R A FrankS M Sorensen

Abstract

Recent experiments have demonstrated that 5-HT2A antagonists can modify electrophysiological, neurochemical, and behavioral responses to psychostimulants. These findings led to an interest in using 5-HT2A antagonists to block the effects of psychostimulants on brain reward mechanisms. The present experiments assessed the ability of mixed D2/5-HT2A antagonists to reverse amphetamine-induced facilitation of self-stimulation. The D2/5-HT2A antagonists MDL 28,133A and risperidone attenuated the effects of cocaine and amphetamine, but only at antagonist doses that elevated baseline self-stimulation thresholds. A comparison of the effects of the mixed antagonists to those of haloperidol and eticlopride revealed that all four antagonists produced similar anti-stimulant effects when the influence of the drugs on baseline responding was considered. The D2 activity of the antagonists appears to account for their ability to reduce the effects of psychostimulants on self-stimulation. 5-HT2A antagonism makes a negligible contribution to the anti-amphetamine effects.

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Citations

Dec 23, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Patricia A BroderickYueping Zhou
Sep 23, 1997·Pharmacology, Biochemistry, and Behavior·D J FeldmanS Shah
Feb 26, 1998·Pharmacology, Biochemistry, and Behavior·V L TsibulskyR A Frank
Dec 27, 2008·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Maria MavrikakiGeorge Panagis

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