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Interactions between CB1 cannabinoid and mu opioid receptors mediating inhibition of neurotransmitter release in rat nucleus accumbens core.
Neuropharmacology. 2006 Sep; 51(4):773-81.N

Abstract

We examined the occurrence of functional interactions between CB1 cannabinoid and mu opioid receptors in the core of rat nucleus accumbens (NAc core). To that end, receptor-mediated inhibition of depolarization (4-aminopyridine)-induced [3H]glutamate release and glutamate (NMDA) receptor-stimulated [14C]acetylcholine (ACh) and [3H]GABA release was studied in superfused NAc core slices. The inhibitory effects of the mu receptor agonist morphine and the CB1 receptor agonist HU210 on the release of these neurotransmitters were selectively antagonized by the mu receptor antagonist naloxone and the CB1 receptor antagonist SR141716A, respectively. Surprisingly, naloxone prevented the antagonistic action of SR141716A at CB1 receptors and SR141716A abolished that of naloxone at mu receptors mediating inhibition of [3H]glutamate and [3H]GABA release. Therefore, these antagonists seem to allosterically interact, indicating the involvement of physically associated mu opioid and CB1 cannabinoid receptors. Such an interaction between antagonists was not observed at the receptors mediating inhibition of [14C]ACh release. Moreover, dose-response curves of the agonists showed that mu and CB1 receptors mediating inhibition of [3H]glutamate release display a non-additive interaction, whereas these receptors synergistically interact regarding their inhibitory control of [3H]GABA release. Finally, the apparent allosteric interaction between antagonists was also observed regarding the effects of other receptor-selective agonists and antagonists at mu opioid and CB1 cannabinoid receptors (mediating inhibition of NMDA-induced [3H]GABA release) and must therefore be a unique property of the receptors involved. These data suggest the existence of physically associated mu opioid and CB1 cannabinoid receptors, whereby activation of these receptors results in either a non-additive (glutamate release) or a synergistic (GABA release) effect. It is proposed that these allosterically interacting mu and CB1 receptors in the NAc core may represent G-protein coupled heterodimeric receptor complexes.

Authors+Show Affiliations

Department of Anatomy and Neurosciences, Institute for Clinical and Experimental Neurosciences, VU medical center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. anm.schoffelmeer@vumc.nlNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16806307

Citation

Schoffelmeer, A N M., et al. "Interactions Between CB1 Cannabinoid and Mu Opioid Receptors Mediating Inhibition of Neurotransmitter Release in Rat Nucleus Accumbens Core." Neuropharmacology, vol. 51, no. 4, 2006, pp. 773-81.
Schoffelmeer AN, Hogenboom F, Wardeh G, et al. Interactions between CB1 cannabinoid and mu opioid receptors mediating inhibition of neurotransmitter release in rat nucleus accumbens core. Neuropharmacology. 2006;51(4):773-81.
Schoffelmeer, A. N., Hogenboom, F., Wardeh, G., & De Vries, T. J. (2006). Interactions between CB1 cannabinoid and mu opioid receptors mediating inhibition of neurotransmitter release in rat nucleus accumbens core. Neuropharmacology, 51(4), 773-81.
Schoffelmeer AN, et al. Interactions Between CB1 Cannabinoid and Mu Opioid Receptors Mediating Inhibition of Neurotransmitter Release in Rat Nucleus Accumbens Core. Neuropharmacology. 2006;51(4):773-81. PubMed PMID: 16806307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactions between CB1 cannabinoid and mu opioid receptors mediating inhibition of neurotransmitter release in rat nucleus accumbens core. AU - Schoffelmeer,A N M, AU - Hogenboom,F, AU - Wardeh,G, AU - De Vries,T J, Y1 - 2006/06/30/ PY - 2005/11/23/received PY - 2006/05/17/revised PY - 2006/05/17/accepted PY - 2006/6/30/pubmed PY - 2006/11/7/medline PY - 2006/6/30/entrez SP - 773 EP - 81 JF - Neuropharmacology JO - Neuropharmacology VL - 51 IS - 4 N2 - We examined the occurrence of functional interactions between CB1 cannabinoid and mu opioid receptors in the core of rat nucleus accumbens (NAc core). To that end, receptor-mediated inhibition of depolarization (4-aminopyridine)-induced [3H]glutamate release and glutamate (NMDA) receptor-stimulated [14C]acetylcholine (ACh) and [3H]GABA release was studied in superfused NAc core slices. The inhibitory effects of the mu receptor agonist morphine and the CB1 receptor agonist HU210 on the release of these neurotransmitters were selectively antagonized by the mu receptor antagonist naloxone and the CB1 receptor antagonist SR141716A, respectively. Surprisingly, naloxone prevented the antagonistic action of SR141716A at CB1 receptors and SR141716A abolished that of naloxone at mu receptors mediating inhibition of [3H]glutamate and [3H]GABA release. Therefore, these antagonists seem to allosterically interact, indicating the involvement of physically associated mu opioid and CB1 cannabinoid receptors. Such an interaction between antagonists was not observed at the receptors mediating inhibition of [14C]ACh release. Moreover, dose-response curves of the agonists showed that mu and CB1 receptors mediating inhibition of [3H]glutamate release display a non-additive interaction, whereas these receptors synergistically interact regarding their inhibitory control of [3H]GABA release. Finally, the apparent allosteric interaction between antagonists was also observed regarding the effects of other receptor-selective agonists and antagonists at mu opioid and CB1 cannabinoid receptors (mediating inhibition of NMDA-induced [3H]GABA release) and must therefore be a unique property of the receptors involved. These data suggest the existence of physically associated mu opioid and CB1 cannabinoid receptors, whereby activation of these receptors results in either a non-additive (glutamate release) or a synergistic (GABA release) effect. It is proposed that these allosterically interacting mu and CB1 receptors in the NAc core may represent G-protein coupled heterodimeric receptor complexes. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/16806307/Interactions_between_CB1_cannabinoid_and_mu_opioid_receptors_mediating_inhibition_of_neurotransmitter_release_in_rat_nucleus_accumbens_core_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(06)00144-4 DB - PRIME DP - Unbound Medicine ER -