Dopamine D(2) receptor antagonists prevent delta(9)-tetrahydrocannabinol-induced antinociception in rats

Eur J Pharmacol. 1999 Nov 19;384(2-3):153-6. doi: 10.1016/s0014-2999(99)00696-2.

Abstract

Delta(9)-Tetrahydrocannabinol (1 and 5 mg/kg, i.p.) produced, dose-dependently, antinociceptive effects using hot plate and tail flick tests in rats. These effects were suppressed not only by the cannabinoid CB(1) receptor antagonist SR 141716A (0.5 mg/kg; i.p.) but also by the dopamine D(2) receptor antagonists S(-)-sulpiride (5 and 10 mg/kg; i.p.) and S(-)-raclopride (1.5 and 3 mg/kg; i.p.). Conversely, Delta(9)-tetrahydrocannabinol antinociceptive effects were potentiated by the dopamine D(2) receptor agonists (-)-quinpirole (0.025 mg/kg, s.c.) and (+)-bromocriptine (0.5 and 1 mg/kg; i.p.). Our results indicate that the antinociceptive effects of Delta(9)-tetrahydrocannabinol are mediated by the concomitant activation of cannabinoid CB(1) and dopamine D(2) receptors and that dopamine D(2) receptor agonists may be useful in improving the analgesic effects of cannabinoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology*
  • Animals
  • Bromocriptine / pharmacology
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Dopamine D2 Receptor Antagonists*
  • Dronabinol / pharmacology*
  • Male
  • Nociceptors / drug effects*
  • Pain / prevention & control
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Quinpirole / pharmacology
  • Raclopride / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / agonists
  • Rimonabant
  • Sulpiride / pharmacology

Substances

  • Analgesics, Non-Narcotic
  • Dopamine Agonists
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Piperidines
  • Pyrazoles
  • Receptors, Dopamine D2
  • Quinpirole
  • Bromocriptine
  • Raclopride
  • Dronabinol
  • Sulpiride
  • Rimonabant