Details

Autor(en) / Beteiligte

• NESTBY, P
• TJON, G. H. K
• VISSER, D. T. M
• DRUKARCH, B
• LEYSEN, J. E
• MULDER, A. H
• SCHOFFELMEER, A. N. M

Titel

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

Ist Teil von

• European journal of pharmacology, 1995-12, Vol.294 (2-3), p.771-777

Ort / Verlag

Amsterdam: Elsevier

Erscheinungsjahr

1995

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• 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.