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

P Nestby, G H Tjon, D T Visser, B Drukarch, J E Leysen, A H Mulder, A N Schoffelmeer

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Abstract

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.

Original languageEnglish
Pages (from-to)771-7
Number of pages7
JournalEuropean Journal of Pharmacology
Volume294
Issue number2-3
Publication statusPublished - 29 Dec 1995

Cite this

Nestby, P., Tjon, G. H., Visser, D. T., Drukarch, B., Leysen, J. E., Mulder, A. H., & Schoffelmeer, A. N. (1995). Intermittent morphine treatment causes long-term desensitization of functional dopamine D2 receptors in rat striatum. European Journal of Pharmacology, 294(2-3), 771-7.