Chronic antipsychotic treatment selectively alters nerve growth factor and neuropeptide Y immunoreactivity and the distribution of choline acetyl transferase in rat brain regions.

ABSTRACT

Neuropeptides and neurotrophins play a number of roles in the central nervous system (CNS). Nerve growth factor (NGF), the first characterized member of the family of neurotrophins, influences the synthesis of some neuropeptides, including neuropeptide Y (NPY), a peptide amply expressed in the CNS, interacting with catecholamines and modifying behaviour. In this study we investigated whether antipsychotic treatment affects the constitutive levels of NGF-, NPY- and choline acetyl transferase (ChAT)-like immunoreactivities (-LI) in the CNS. Rats were fed food supplemented with haloperidol (1.15 mg/100 g food), risperidone (1.15 or 2.3 mg/100 g food), or vehicle. After 29 d treatment animals were sacrificed with focused high-energy microwave irradiation for radioimmunoassay (RIA) of NPY-LI, by decapitation for analysis of NGF, and by perfusion for immunocytochemistry. Haloperidol and risperidone elevated NGF-LI concentrations in the hypothalamus but decreased NGF-LI in the striatum and hippocampus. In contrast, antipsychotics did not alter NPY-LI in the striatum. Haloperidol increased NPY-LI concentration in the occipital cortex, while risperidone increased NPY-LI in the occipital cortex, hippocampus, and hypothalamus. Significant decreases in ChAT immunoreactivity in large-size neurons following both haloperidol and risperidone treatments in the septum as well as Meynert's nucleus were observed. Our findings demonstrate that antipsychotic drugs alter the regional brain levels of NGF-LI, NPY-LI and ChAT-LI and raise the possibility that these effects are implicated in their pharmacological and therapeutic properties.