title: Memory encoding in hippocampal ensembles is negatively influenced by cannabinoid CB1 receptors.
abstract: It has previously been demonstrated that the detrimental effect on the performance of a delayed nonmatch to sample (DNMS) memory task by exogenously administered cannabinoid (CB1) receptor agonist, WIN 55212-2 (WIN), is reversed by the receptor antagonist rimonabant. In addition, rimonabant administered alone elevates DNMS performance, presumably through the suppression of negative modulation by released endocannabinoids during normal task performance. Other investigations have shown that rimonabant enhances encoding of DNMS task-relevant information on a trial-by-trial, delay-dependent basis. In this study, these reciprocal pharmacological actions were completely characterized by long-term, chronic intrahippocampal infusion of both agents (WIN and rimonabant) in successive 2-week intervals. Such long-term exposure allowed extraction and confirmation of task-related firing patterns, in which rimonabant reversed the effects of CB1 agonists. This information was then utilized to artificially impose the facilitatory effects of rimonabant and to reverse the effects of WIN on DNMS performance, by delivering multichannel electrical stimulation in the same firing patterns to the same hippocampal regions. Direct comparison of normal and WIN-injected subjects, in which rimonabant injections and ensemble firing facilitated performance, verified reversal of the modulation of hippocampal memory processes by CB1 receptor agonists, including released endocannabinoids.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hampson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sweatt
authors.forename: Anushka V
authors.initials: AV
authors.lastname: Goonawardena
authors.forename: Dong
authors.initials: D
authors.lastname: Song
authors.forename: Rosa H M
authors.initials: RH
authors.lastname: Chan
authors.forename: Vasilis Z
authors.initials: VZ
authors.lastname: Marmarelis
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Berger
authors.forename: Sam A
authors.initials: SA
authors.lastname: Deadwyler
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D048588:Benzoxazines / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects; D002186:Cannabinoids / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007267:Injections; D008297:Male; D008568:Memory / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D000077285:Rimonabant
chemical_list: D001549:Benzamides; D048588:Benzoxazines; D001713:Biphenyl Compounds; D002186:Cannabinoids; D002219:Carbamates; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C501835:URB602; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant