Effects of haloperidol and clozapine on neuropeptide Y-like immunoreactivity in the nucleus accumbens and striatum of rats pretreated with psychostimulants

Abstract

It has been shown that the synthesis, release and levels of neuropeptide Y (NPY), a peptide linked to the dopamine system, are altered by stimulants with psychotomimetic properties and by antipsychotic drugs. This study was designed to evaluate the effect of 3-day haloperidol (HAL) (2 mg/kg i.p.) or clozapine (CLOZ) (25 mg/kg i.p.) treatment on neuropeptide Y-like immunoreactivity (NPY-LI) in nucleus accumbens and striatum (caudate-putamen) in rats pretreated with d-amphetamine or phencyclidine. D-amphetamine (5 mg/kg s.c. twice daily for 6 days and once on day 7) and phencyclidine (10 mg/kg i.p. once daily for 2 days and 15 mg/kg once on day 3) induced marked stereotypy with different symptomatology. Stereotypy is thought to resemble psychosis-related behavior. The first dose of either HAL or CLOZ was given 3 or 2 h after the final d-amphetamine or phencyclidine injection, respectively. The control groups were injected with either saline alone, saline instead of psychostimulants, which was followed by antipsychotics, or psychostimulants followed by saline. Rats were sacrificed 24 h after antipsychotics or 72 h after the last psychostimulant dose. Both psychostimulants similarly reduced nucleus accumbens and striatal NPY-LI. In saline-pretreated rats, HAL and CLOZ decreased nucleus accumbens NPY-LI, but only HAL decreased striatal NPY-LI. In both the structures examined the effects of HAL and d-amphetamine on NPY-LI were additive. HAL slightly enhanced but CLOZ reversed the phencyclidine-induced decrease in accumbens NPY-LI. The present study has shown that HAL and CLOZ produce different effects on nucleus accumbens and striatal NPY-LI in d-amphetamine or phencyclidine pretreated rats, and it suggests that these effects are related particularly to the dopaminergic and glutamatergic systems whose activities were altered by psychostimulants.