Dopamine receptor antagonists prevent expression, but not development, of morphine sensitization

Eur J Pharmacol. 1995 Mar 14;275(3):235-44. doi: 10.1016/0014-2999(94)00779-7.

Abstract

The present experiments determined the effects of selective dopamine receptor antagonists on the initiation and expression of sensitization to the locomotor-stimulating effects of morphine in rats. Although both the dopamine D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaz epine hydrochloride (SCH 23390, 0.25 mg/kg) and the dopamine D2 receptor antagonist eticlopride (0.1 mg/kg) suppressed the ability of morphine (10 mg/kg) to elicit sensitized locomotor activity during the course of a 12 day treatment schedule, subsequent tests with morphine alone revealed significant sensitization. Sensitization in the SCH 23390 + morphine group could not be attributed to dopamine D1 receptor supersensitivity caused by repeated SCH 23390 administration because electrophysiological recordings indicated that nucleus accumbens neurons in SCH 23390-treated rats were not more sensitive to the inhibitory effects of either dopamine or a dopamine D1 receptor-selective agonist. Thus, dopamine receptor stimulation may be involved in expression, but not development, of morphine sensitization.

Publication types

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

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Dopamine Antagonists / pharmacology*
  • Dopamine D2 Receptor Antagonists*
  • Male
  • Morphine / pharmacology*
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Salicylamides / pharmacology

Substances

  • Benzazepines
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine D1
  • Receptors, N-Methyl-D-Aspartate
  • Salicylamides
  • Morphine
  • eticlopride