Intermittent morphine treatment causes long-term desensitization of functional dopamine D2 receptors in rat striatum

Eur J Pharmacol. 1995 Dec 29;294(2-3):771-7. doi: 10.1016/0014-2999(95)00631-1.


3 weeks following cessation of intermittent morphine administration (10 mg/kg, s.c., once daily for 14 days), [3H]dopamine and [14C]acetylcholine release induced by 10 microM N-methyl-D-aspartate (NMDA) from superfused rat striatal slices appeared to be significantly higher than the release from striatal slices from saline-treated rats. A similar adaptive increase of the NMDA-evoked release of these neurotransmitters was observed in slices of the nucleus accumbens, whereas that of [3H]noradrenaline from hippocampal slices remained unchanged. Blockade of dopamine D2 receptors by 10 microM (--)-sulpiride enhanced NMDA-induced [3H]dopamine and [14C]acetylcholine release from striatal slices from saline-treated animals, but was found to be ineffective in this respect following intermittent morphine treatment. Moreover, morphine administration appeared to cause a profound decrease in the apparent affinity of the full dopamine D2 receptor agonist LY171555 (quinpirole) for these release-inhibitory dopamine D2 receptors, indicating the occurrence of dopamine D2 receptor desensitization. It is suggested that such a desensitization of dopamine D2 receptors on dopaminergic nerve terminals as well as on cholinergic interneurons may play a pivotal role in the long-lasting nature of behavioural sensitization upon cessation of treatment with morphine and possibly other drugs of abuse.

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Corpus Striatum / drug effects*
  • Dopamine / metabolism
  • In Vitro Techniques
  • Male
  • Morphine / pharmacology*
  • N-Methylaspartate / pharmacology
  • Narcotics / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / drug effects*
  • Sulpiride / pharmacology


  • Narcotics
  • Receptors, Dopamine D2
  • N-Methylaspartate
  • Morphine
  • Sulpiride
  • Acetylcholine
  • Dopamine