title: Cannabinoid regulation in identified synapse of terrestrial snail.
abstract: In the terrestrial snail a direct monosynaptic glutamatergic connection between the primary sensory neuron and a premotor interneuron involved in withdrawal behaviour can be functionally identified using electrophysiological techniques. We investigated the involvement of cannabinoids in regulation of this synaptic contact. The results demonstrate that the specific binding sites for agonists to mammalian type 1 cannabinoid receptors (CB1Rs) exist in the snail's nervous system. Application of a synthetic cannabinoid agonist anandamide selectively changed the efficacy of synaptic contacts between the identified neurons. A decrease in the long-term synaptic facilitation of the synaptic contact elicited by high-frequency nerve tetanization in the presence of cannabinoid agonist anandamide was observed, suggesting a possible role of endocannabinoids in regulation of plasticity at this synaptic site. The selective antagonist of CB1Rs [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] AM251 bath application was changing the efficacy of the synaptic contact only when the postsynaptic neuron had been intracellularly activated before its application. This observation implies an involvement of endocannabinoids in plasticity phenomena induced by activity in the postsynaptic target. Additional support of endocannabinoid involvement in synaptic function at this site was given by experiments in which AM251 blocked the short-term suppression of synaptic excitation evoked by low-frequency nerve tetanization, a phenomenon qualitatively similar to cannabinoid-dependent synaptically evoked suppression of excitation demonstrated in the mammalian nervous system. The results of the present study suggest an involvement of cannabinoids in the regulation of synaptic efficacy. Further, anandamide could be a candidate for an endogenous neuromessenger involved in plasticity processes.
authors.affiliation: Department of Cellular Neurobiology, Institute of Higher Nervous Activity and Neurophysiology RAS, Moscow, Russia.
authors.forename: M S
authors.initials: MS
authors.lastname: Lemak
authors.forename: N I
authors.initials: NI
authors.lastname: Bravarenko
authors.forename: M Yu
authors.initials: MY
authors.lastname: Bobrov
authors.forename: V V
authors.initials: VV
authors.lastname: Bezuglov
authors.forename: V N
authors.initials: VN
authors.lastname: Ierusalimsky
authors.forename: M V
authors.initials: MV
authors.lastname: Storozhuk
authors.forename: A Y
authors.initials: AY
authors.lastname: Malyshev
authors.forename: P M
authors.initials: PM
authors.lastname: Balaban
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D002186:Cannabinoids / Q000378:metabolism*; D003511:Cyclohexanols / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D063388:Endocannabinoids; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009420:Nervous System / Q000166:cytology; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D012908:Snails / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014316:Tritium / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D003511:Cyclohexanols; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D014316:Tritium; C103505:AM 251; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C078814:anandamide