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.