P.3.d.010 Antipsychotic drugs induce dopamine type 2 receptor mediated suppression of neuronal firing in the rat nucleus incertus

Abstract

Noncompetitive N-methyl-d-aspartate receptor antagonists, including phencyclidine (PCP; also called angel dust), can cause abnormal behaviors. Among PCP-induced abnormal behaviors, we have focused on the mechanisms of hyperlocomotion and motor impairment. Studies have reported that serotonergic neurotoxin lesions of the median raphe nucleus induce significant enhancement of PCP-induced hyperlocomotion and higher levels of PCP-induced Fos immunoreactivity. Cortical cholinergic hypofunction also leads to enhanced PCP-induced locomotor activity. By contrast, ablation of the glutamate GluN2D subunit attenuates PCP-induced hyperlocomotion, behavioral sensitization, and motor impairment. The number of Fos-positive cells increases after PCP administration in the basal ganglia motor circuit in wild type mice but not in GluN2D knock out mice, suggesting that the GluN2D subunit within the motor circuitry is a key component of PCP-induced motor impairment. These results suggest that serotonergic, cholinergic, and glutamatergic innervations play important roles in PCP-induced abnormal behavior.