The dopamine D4 receptor antagonist L-745,870: effects in rats discriminating cocaine from saline

Eur J Pharmacol. 1998 Mar 19;345(2):129-32. doi: 10.1016/s0014-2999(97)01603-8.

Abstract

The contribution of dopamine D4 receptors to the discriminative stimulus effects of cocaine was evaluated by testing the selective dopamine D4 receptor antagonist, L-745,870 (3-([4-(4-chlororphenyl) piperazin-1-yl] methyl)-1 H-pyrrolo[2,3-b] pyridine), alone and in combination with cocaine, in rats trained to discriminate cocaine (10 mg/kg) from saline. The antagonist (1-10 mg/kg) failed to engender cocaine-appropriate responding when injected alone, and failed to modify the cocaine dose-response curve when injected as a pre-treatment; however, it reduced response rates dose-dependently. Conversely, the dopamine 'D1-like' receptor antagonist, SCH 39166 ((-)-trans-6,7,7a,8,9, 13b-hexahydro-3-chloro-2hydroxy-N-methyl-5H-benzo[d]napth o-¿2,1-b¿azepine, produced surmountable antagonism. Results suggest that dopamine D4 receptors play a negligible role in cocaine's discriminative stimulus effects, and further support a critical involvement of dopamine D1-like receptors.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cocaine / administration & dosage*
  • Conditioning, Operant / drug effects
  • Discrimination, Psychological / drug effects*
  • Dopamine Antagonists / pharmacology*
  • Male
  • Pyridines / pharmacology*
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / physiology
  • Receptors, Dopamine D4

Substances

  • 3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine
  • Dopamine Antagonists
  • Drd4 protein, rat
  • Pyridines
  • Pyrroles
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • Cocaine