Time dependent decreases in central alpha7 nicotinic acetylcholine receptors associated with haloperidol and risperidone treatment in rats

Alpha(7) nicotinic acetylcholine receptor deficits may contribute to cognitive dysfunction in schizophrenia; however, the contribution of antipsychotic drug exposure to these deficits is unknown. In this study, rats were treated orally with haloperidol (2.0 mg/kg/day) or risperidone (2.5 mg/kg/day) for 15 or 90 days. Subsequent immunoassays indicated that both antipsychotics were associated with alpha(7) nicotinic receptor decreases in the basal forebrain and prefrontal cortex when administered for 90 (but not 15) days, a result that was confirmed in autoradiographic experiments. These data suggest that haloperidol and risperidone may be associated with time dependent decreases in an important neurobiological substrate of memory.