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Presynaptic α₂-adrenoceptors control the inhibitory action of presynaptic CB₁ cannabinoid receptors on prefrontocortical norepinephrine release in the rat.
Neuropharmacology. 2012 Oct; 63(5):784-97.N

Abstract

Endocannabinoids play a crucial neuromodulator role in both physiological and pathological states in various brain regions including the prefrontal cortex (PFC). We examined, whether presynaptic cannabinoid receptors are involved in the modulation of basal and electrical field stimulation-evoked [³H]norepinephrine ([³H]NE) release from rat PFC slices. WIN55,212-2, a nonselective CB₁ receptor (CB₁R) agonist, inhibited the electrical stimulation-evoked efflux of [³H]NE in a concentration-dependent fashion, which was antagonized by the CB₁R antagonist/inverse agonist, AM251 (1 μM). Idazoxan, a selective α₂-adrenoceptor antagonist, augmented the evoked [³H]NE release. In the presence of idazoxan, the effect of WIN55,212-2 was exacerbated or attenuated, depending on the applied concentration and stimulation frequency. Moreover their combined, but not individual application elicited a depressive-like phenomenon in the forced-swim test. These data were bolstered with fluorescent and confocal microscopy analysis, which revealed that CB₁R immunoreactivity co-localized with dopamine-β-hydroxylase positive (i.e. noradrenergic) fibers and the inhibitory α(2A) adrenergic autoreceptors (α(2A)R) in the PFC. Furthermore, idazoxan triggered a decrease in CB₁R density in the PFC, suggesting that high extracellular level of norepinephrine downregulates CB₁Rs.

Authors+Show Affiliations

Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences-IEM-HAS, H-1083 Budapest, Szigony U. 43, Hungary.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22722024

Citation

Richter, Hardy, et al. "Presynaptic Α₂-adrenoceptors Control the Inhibitory Action of Presynaptic CB₁ Cannabinoid Receptors On Prefrontocortical Norepinephrine Release in the Rat." Neuropharmacology, vol. 63, no. 5, 2012, pp. 784-97.
Richter H, Teixeira FM, Ferreira SG, et al. Presynaptic α₂-adrenoceptors control the inhibitory action of presynaptic CB₁ cannabinoid receptors on prefrontocortical norepinephrine release in the rat. Neuropharmacology. 2012;63(5):784-97.
Richter, H., Teixeira, F. M., Ferreira, S. G., Kittel, Á., Köfalvi, A., & Sperlágh, B. (2012). Presynaptic α₂-adrenoceptors control the inhibitory action of presynaptic CB₁ cannabinoid receptors on prefrontocortical norepinephrine release in the rat. Neuropharmacology, 63(5), 784-97. https://doi.org/10.1016/j.neuropharm.2012.06.003
Richter H, et al. Presynaptic Α₂-adrenoceptors Control the Inhibitory Action of Presynaptic CB₁ Cannabinoid Receptors On Prefrontocortical Norepinephrine Release in the Rat. Neuropharmacology. 2012;63(5):784-97. PubMed PMID: 22722024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Presynaptic α₂-adrenoceptors control the inhibitory action of presynaptic CB₁ cannabinoid receptors on prefrontocortical norepinephrine release in the rat. AU - Richter,Hardy, AU - Teixeira,Filipe M, AU - Ferreira,Samira G, AU - Kittel,Ágnes, AU - Köfalvi,Attila, AU - Sperlágh,Beáta, Y1 - 2012/06/18/ PY - 2011/11/17/received PY - 2012/05/15/revised PY - 2012/06/05/accepted PY - 2012/6/23/entrez PY - 2012/6/23/pubmed PY - 2013/1/15/medline SP - 784 EP - 97 JF - Neuropharmacology JO - Neuropharmacology VL - 63 IS - 5 N2 - Endocannabinoids play a crucial neuromodulator role in both physiological and pathological states in various brain regions including the prefrontal cortex (PFC). We examined, whether presynaptic cannabinoid receptors are involved in the modulation of basal and electrical field stimulation-evoked [³H]norepinephrine ([³H]NE) release from rat PFC slices. WIN55,212-2, a nonselective CB₁ receptor (CB₁R) agonist, inhibited the electrical stimulation-evoked efflux of [³H]NE in a concentration-dependent fashion, which was antagonized by the CB₁R antagonist/inverse agonist, AM251 (1 μM). Idazoxan, a selective α₂-adrenoceptor antagonist, augmented the evoked [³H]NE release. In the presence of idazoxan, the effect of WIN55,212-2 was exacerbated or attenuated, depending on the applied concentration and stimulation frequency. Moreover their combined, but not individual application elicited a depressive-like phenomenon in the forced-swim test. These data were bolstered with fluorescent and confocal microscopy analysis, which revealed that CB₁R immunoreactivity co-localized with dopamine-β-hydroxylase positive (i.e. noradrenergic) fibers and the inhibitory α(2A) adrenergic autoreceptors (α(2A)R) in the PFC. Furthermore, idazoxan triggered a decrease in CB₁R density in the PFC, suggesting that high extracellular level of norepinephrine downregulates CB₁Rs. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/22722024/Presynaptic_α₂_adrenoceptors_control_the_inhibitory_action_of_presynaptic_CB₁_cannabinoid_receptors_on_prefrontocortical_norepinephrine_release_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(12)00261-4 DB - PRIME DP - Unbound Medicine ER -