MIXED D-2 5-HT2 ANTAGONISM DIFFERENTIALLY AFFECTS APOMORPHINE-INDUCEDAND AMPHETAMINE-INDUCED STEREOTYPED BEHAVIOR/

Evidence supports the hypothesis that psychostimulant stereotypy is me diated through postsynaptic dopamine receptors. Given the recent findi ngs of behavioral, neurochemical and electrophysiological studies show ing 5-HT2 modulation of dopamine systems, a series of experiments were undertaken to assess the ability of D-2 and 5-HT2 antagonists to reve rse apomorphine and amphetamine stereotypy in the rat. Haloperidol red uced stereotyped behavior induced by d-amphetamine (50% reduction with 0.162 mg/kg) and apomorphine (50% reduction with 0.112 mg/kg) MDL 28, 133A, a mixed D-2/5-HT2 antagonist, also reduced stereotypy in the apo morphine group (50% reduction with 3.89 mg/kg) but was much less effec tive in antagonizing the effects of d-amphetamine (not even a 25% redu ction with 9.0 mg/kg). MDL 100,907, a selective 5-HT2 antagonist, was ineffective at reducing stereotyped behavior induced by either stimula nt. Thus, 5-HT2 modulation of dopaminergic activity was not demonstrat ed in the case of psychostimulant stereotypy. Furthermore, 5-HT2 antag onism did not induce stereotypy, as has been proposed in some models. These findings provide further support for the hypothesis that antipsy chotic medications with high affinity for 5-HT2 receptors do not inter fere with the regulation of the nigrostriatal dopaminergic system and, therefore, would be less likely to produce extrapyramidal side effect s. (C) 1997 Elsevier Science Inc.