Role of dopamine D1 and D2 receptors in CRF-induced disruption of sensorimotor gating

Corticotropin-releasing factor (CRF), a neuropeptide released during stress, has been reported to modulate startle behavior, including reducing the threshold for acoustic startle responding and reducing prepulse inhibition (PPI). The central mechanisms mediating CRF system regulation of startle and PPI are still unclear. Some antipsychotic drugs attenuate CRF-induced deficits in PPI in rats and mice. Here we tested the hypothesis that indirect activation of DA1-receptors (D1) and DA2-receptors (D2) contributes to the effects of CRF on PPI. We compared the effect of central administration of h/r-CRF (0.2–0.6 nmol) on PPI in mice with either a D1 or D2 receptor null mutation (knockout, KO) or in mice pretreated with D1 or D2 receptor antagonists SCH23390 (1 mg/kg) or haloperidol (1 mg/kg). D1 and D2 KO mice exhibited no significant differences in their sensitivity to CRF-induced disruptions of PPI. Similarly, neither SCH23390 nor haloperidol pretreatment altered the CRF-induced disruption in PPI, although both increased PPI at baseline. CRF-induced increases in startle also remained unchanged by any of the DA receptor manipulations. These results indicate that neither D1- nor D2-receptor activation is necessary for CRF to exert its effects on acoustic startle and PPI in mice.