Multiple Nicotinic Acetylcholine Receptor Subtypes Regulate Social Or Cognitive Behaviors In Mice Repeatedly Administered Phencyclidine

Habitual smoking in patients with schizophrenia (SCZ) is considered to improve their own psychoses or to develop a vulnerability to psychological dependence on (-)-nicotine ([-]-NIC) by stimulating nicotinic acetyl -choline receptors (nAChRs) in the central nervous system. In the present study, we investigated whether habitual smoking is due to get therapeutic effect or to psychological dependence and which nAChR subunits are asso-ciated with them using mice that were repeatedly administered phencyclidine (PCP: 10 mg/kg/day, s.c. for 14 days) as SCZ-like model mice. Mice that were repeatedly administered PCP showed impairments in social or cognitive behaviors; decreased expression of ?7 and/or ?4 nAChR subunits in the prefrontal cortex (PFC); and increased expression of ?7, ?4, and 82 nAChR subunits in the nucleus accumbens (NAc). These changes were attenuated by repeated administration of (-)-NIC. The attenuating effects on behavioral impairments were pre-vented by a selective ?7 nAChR antagonist and a selective ?482 nAChR antagonist. At non-or weak effective dose by themselves, co-administration of (-)-NIC (0.03 mg/kg) and risperidone (0.03 mg/kg) showed synergistic ef-fects on behavioral impairments in PCP-administered mice. Repeated (-)-NIC administration did not affect the performance of conditioned place preference, while it showed behavioral sensitization to (-)-NIC in the PCP-administered mice. Repeated (-)-NIC administration did not affect the performance of conditioned place pref-erence, while it showed behavioral sensitization to (-)-NIC and attenuating effect on haloperidol-induced cata-lepsy in the PCP-administered mice. Our findings suggest that habitual smoking in SCZ might be attributed to get therapeutic and reduce side effects mediated by ?7 and ?482 nAChR activation by (-)-NIC.