Dopamine agonist-induced hypothermia and disruption of prepulse inhibition: evidence for a role of D3 receptors?

Behav Pharmacol. 1998 Sep;9(5-6):445-55. doi: 10.1097/00008877-199809000-00008.

Abstract

The dopamine D3/D2 receptor agonists 7-OH-DPAT, quinpirole, quinelorane, and PD128907, the mixed dopamine agonist apomorphine, the D2 agonist bromocriptine, and the D1/D5 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 D3 receptor function, and dopamine agonists are known to disrupt PPI, drug potencies to induce hypothermia were established and compared with 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 ineffective in both models. In a separate study, the dopamine reuptake inhibitors cocaine and GBR 12909 had no effect on PPI. In a final set of studies, the D2/D3 antagonist raclopride blocked both 7-OH-DPAT-induced hypothermia and 7-OH-DPAT-induced PPI disruption. The 5-HT1A antagonist WAY 100,135, and the peripheral D2-like antagonist domperidone had no effect. These findings suggest that the hypothermia and PPI disruptions seen with some of these dopamine agonists may be mediated by central D3 receptors; however, only studies using more selective dopamine receptor ligands can definitively rule out effects at the D2 or D4 receptors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Temperature / drug effects
  • Cocaine / pharmacology
  • Domperidone / pharmacology
  • Dopamine Agonists / pharmacology*
  • Dopamine Antagonists / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • Hypothermia / chemically induced*
  • Hypothermia / physiopathology*
  • Male
  • Piperazines / pharmacology
  • Raclopride
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / physiology*
  • Receptors, Dopamine D3
  • Reflex, Startle / drug effects*
  • Salicylamides / pharmacology
  • Serotonin Antagonists / pharmacology

Substances

  • Dopamine Agonists
  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Drd3 protein, rat
  • Piperazines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Salicylamides
  • Serotonin Antagonists
  • WAY 100135
  • Raclopride
  • Domperidone
  • vanoxerine
  • Cocaine