title: Neurophysiological evidence for the presence of cannabinoid CB1 receptors in the laterodorsal tegmental nucleus.
abstract: Marijuana, which acts within the endocannabinoid (eCB) system as an agonist of the cannabinoid type 1 receptor (CB1R), exhibits addictive properties and has powerful actions on the state of arousal of an organism. The laterodorsal tegmental nucleus (LDT), as a component of the reticular activating system, is involved in cortical activation and is important in the development of drug addiction-associated behaviours. Therefore, eCBs might exert behavioural effects by actions on the LDT; however, it is unknown whether eCBs have actions on neurons in this nucleus. Accordingly, whole-cell voltage- and current-clamp recordings were conducted from mouse brain slices, and responses of LDT neurons to the CB1R agonist WIN-2 were monitored. Our results showed that WIN-2 decreased the frequency of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs). Ongoing activity of endogenous eCBs was confirmed as AM251, a potent CB1R antagonist, elicited sIPSCs. WIN-2 reduced the firing frequency of LDT neurons. In addition, our RT-PCR studies confirmed the presence of CB1R transcript in the LDT. Taken together, we conclude that CB1Rs are functionally active in the LDT, and their activation changes the firing frequency and synaptic activity of neurons in this nucleus. Therefore, endogenous eCB transmission could play a role in processes involving the LDT, such as cortical activation and motivated behaviours and, further, behavioural actions of marijuana are probably mediated, in part, via cellular actions within the LDT induced by this addictive and behavioural state-altering drug.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Soni
authors.forename: Shankha
authors.initials: S
authors.lastname: Satpathy
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Kohlmeier
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: C578453:CNR1 protein, mouse; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D011188:Potassium
keywords: arousal; cholinergic; electrophysiology; endocannabinoids; synaptic transmission