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Systemic effect of cannabinoids on the spontaneous firing rate of locus coeruleus neurons in rats.
Eur J Pharmacol. 2006 Mar 18; 534(1-3):83-8.EJ

Abstract

Previous reports have described modulation of noradrenergic activity by cannabinoid receptors. The aim of the present research was to examine the effect of two synthetic cannabinoid CB1/CB2 receptor agonists, R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)-methyl]pyrrolol-[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone (WIN 55212-2) and (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP 55940), on the spontaneous activity of locus coeruleus noradrenergic neurons by single-unit extracellular recordings in vivo and in vitro. In anaesthetized rats, intravenous administrations of WIN 55212-2 (31.3-500 microg/kg) or CP 55940 (31.3-500 microg/kg) increased the firing rate of locus coeruleus neurons in a dose-dependent manner. The stimulatory effect of WIN 55212-2 was blocked by pretreatment with the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR 141716A; 2 mg/kg). Paradoxically, local administration of WIN 55212-2 (8.3-31.3 pmol) into the locus coeruleus and intracerebroventricular injections of WIN 55212-2 (10-20 microg) or CP 55940 (20-40 microg) failed to change the spontaneous firing rate of locus coeruleus neurons. Likewise, in rat brain slice preparations perfusion with WIN 55212-2 (10 microM) or CP 55940 (10-30 microM) did not specifically affect the spontaneous firing rate of locus coeruleus cells. Therefore, we conclude that synthetic cannabinoids increase the spontaneous firing activity of noradrenergic neurons in the rat locus coeruleus through cannabinoid CB1 receptors. This stimulation appears to be indirectly induced via a receptor mechanism probably located at the peripheral level.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medicine, University of the Basque Country, E-48940 Leioa, Bizkaia, Spain.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16483566

Citation

Mendiguren, Aitziber, and Joseba Pineda. "Systemic Effect of Cannabinoids On the Spontaneous Firing Rate of Locus Coeruleus Neurons in Rats." European Journal of Pharmacology, vol. 534, no. 1-3, 2006, pp. 83-8.
Mendiguren A, Pineda J. Systemic effect of cannabinoids on the spontaneous firing rate of locus coeruleus neurons in rats. Eur J Pharmacol. 2006;534(1-3):83-8.
Mendiguren, A., & Pineda, J. (2006). Systemic effect of cannabinoids on the spontaneous firing rate of locus coeruleus neurons in rats. European Journal of Pharmacology, 534(1-3), 83-8.
Mendiguren A, Pineda J. Systemic Effect of Cannabinoids On the Spontaneous Firing Rate of Locus Coeruleus Neurons in Rats. Eur J Pharmacol. 2006 Mar 18;534(1-3):83-8. PubMed PMID: 16483566.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Systemic effect of cannabinoids on the spontaneous firing rate of locus coeruleus neurons in rats. AU - Mendiguren,Aitziber, AU - Pineda,Joseba, Y1 - 2006/02/14/ PY - 2005/11/11/received PY - 2005/12/23/revised PY - 2006/01/04/accepted PY - 2006/2/18/pubmed PY - 2006/6/8/medline PY - 2006/2/18/entrez SP - 83 EP - 8 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 534 IS - 1-3 N2 - Previous reports have described modulation of noradrenergic activity by cannabinoid receptors. The aim of the present research was to examine the effect of two synthetic cannabinoid CB1/CB2 receptor agonists, R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)-methyl]pyrrolol-[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone (WIN 55212-2) and (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP 55940), on the spontaneous activity of locus coeruleus noradrenergic neurons by single-unit extracellular recordings in vivo and in vitro. In anaesthetized rats, intravenous administrations of WIN 55212-2 (31.3-500 microg/kg) or CP 55940 (31.3-500 microg/kg) increased the firing rate of locus coeruleus neurons in a dose-dependent manner. The stimulatory effect of WIN 55212-2 was blocked by pretreatment with the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR 141716A; 2 mg/kg). Paradoxically, local administration of WIN 55212-2 (8.3-31.3 pmol) into the locus coeruleus and intracerebroventricular injections of WIN 55212-2 (10-20 microg) or CP 55940 (20-40 microg) failed to change the spontaneous firing rate of locus coeruleus neurons. Likewise, in rat brain slice preparations perfusion with WIN 55212-2 (10 microM) or CP 55940 (10-30 microM) did not specifically affect the spontaneous firing rate of locus coeruleus cells. Therefore, we conclude that synthetic cannabinoids increase the spontaneous firing activity of noradrenergic neurons in the rat locus coeruleus through cannabinoid CB1 receptors. This stimulation appears to be indirectly induced via a receptor mechanism probably located at the peripheral level. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/16483566/Systemic_effect_of_cannabinoids_on_the_spontaneous_firing_rate_of_locus_coeruleus_neurons_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(06)00004-5 DB - PRIME DP - Unbound Medicine ER -