DOPAMINE AGONIST-INDUCED HYPOTHERMIA AND DISRUPTION OF PREPULSE INHIBITION - EVIDENCE FOR A ROLE OF D-3 RECEPTORS

The dopamine D-3/D-2 receptor agonists 7-OH-DPAT, quinpirole, quinelor ane, and PD128907, the mixed dopamine agonist apomorphine, the D-2 ago nist bromocriptine, and the D-1/D-5 agonist SKF38393 were examined in models of hypothermia and prepulse inhibition (PPI) in Wistar rats. As dopamine agonist-induced hypothermia has been proposed as a model of D-3 receptor function, and dopamine agonists are known to disrupt PPI, drug potencies to induce hypothermia were established and compared wi th doses necessary to disrupt PPI. 7-OH-DPAT, quinpirole, quinelorane, PD128907, and apomorphine, reduced body temperature and disrupted PPI with a similar rank order of potency (quinelorane > quinpirole = 7-OH -DPAT > PD128907 = apomorphine). Bromocriptine and SKF38393 were ineff ective in both models. In a separate study, the dopamine reuptake inhi bitors cocaine and GBR 12909 had no effect on PPI. In a final set of s tudies, the D-2/D-3 antagonist raclopride blocked both 7-OH-DPAT-induc ed hypothermia and 7-OH-DPAT-induced PPI disruption. The 5-HT1A antago nist WAY 100,135, and the peripheral D-2-like antagonist domperidone h ad no effect. These findings suggest that the hypothermia and PPI disr uptions seen with some of these dopamine agonists may be mediated by c entral D-3 receptors; however, only studies using more selective dopam ine receptor ligands can definitively rule out effects at the D-2 or D -4 receptors. Behav Pharmacol 1998; 9:445-455 (C) 1998 Lippincott Will iams & Wilkins.