Effects of antipsychotics and selective D3 antagonists on PPI deficits induced by PD 128907 and apomorphine

Rats treated with apomorphine and amphetamine display sensorimotor gating impairments, as measured by prepulse inhibition (PPI), and these impairments can be reversed by antipsychotic treatment. However, it remains unknown whether the dopamine (DA) D3 receptor plays a role in mediating these effects on PPI, as none of these DA agonists or antipsychotics are exclusively selective at either D2 or D3 receptors. To address this question, the current study was designed to investigate whether antipsychotic drugs and selective D3 antagonists could block the PPI-disruptive effects of PD 128907 (a preferential D3 agonist) and apomorphine. We found that the effect of PD 128907 on PPI in rats could be antagonized by risperidone, clozapine, and the selective D3 antagonists SB 277011 and A-691990, but not by raclopride or haloperidol, while the apomorphine-induced PPI deficit could be reversed by risperidone, clozapine and haloperidol, but not by SB 2770111 and A-691990. These results suggest that the D3 receptor does not mediate apomorphine-induced disruption of PPI in rats, however, given the findings that PD 128907 elicited a PPI-disruptive effect that was blocked by selective D3 antagonists, a role of D3 receptor in mediating PPI in rats cannot be ruled out. The possible mechanisms of D3 receptor involvement in PPI are discussed.