The effect of nicotine and haloperidol co-treatment on nicotinic receptor levels in the rat brain

Genetic and biological data have suggested a role for the neuronal nicotini c acetylcholine receptors in the neuropathophysiology of schizophrenia. Stu dies in human postmortem brain demonstrate dose-dependent increases in nico tinic receptor binding in normal smokers. We found this upregulation to be reduced in schizophrenic smokers, many of whom had taken typical neurolepti cs during their lifetime. The present study examined the hypothesis that ty pical antipsychotic drug treatment might modulate nicotinic receptor upregu lation in a rat model. Nicotine, administered alone or in combination with haloperidol, increased both high and low affinity neuronal nicotinic recept ors in a region specific manner. Haloperidol had no generalized effect on b asal levels of nicotinic receptor binding or nicotine induced upregulation of nicotinic receptors. However, haloperidol attenuated high affinity nicot inic receptor upregulation in thalamus and low affinity receptor upregulati on in hippocampus. These results suggest that haloperidol is not likely to affect nicotinic receptor regulation by smoking in most brain regions. (C) 2001 Elsevier Science B.V. All rights reserved.