title: Post-training CB1 cannabinoid receptor agonist activation disrupts long-term consolidation of spatial memories in the hippocampus.
abstract: Cannabinoids have long been associated with mnemonic deficits. However, existing evidence has generally focused on the effect of cannabinoids when they are delivered prior to task-training, and such findings are confounded by possible drug effects on sensory, motor, and/or motivational systems that support the acquisition and the expression of learning. The present study investigated the effects of the CB1-receptor agonist WIN 55,212-2 (WIN) on memory consolidation in the Morris water maze. In experiment 1, systemic injections of either WIN or DMSO vehicle were given daily following each training day (post-training), and rats were probe-tested 1 week or 4 weeks later. Rats injected with 1 mg/kg and 3 mg/kg of WIN spent significantly less time in the target quadrant compared with controls 4 weeks later, while no difference was observed at 1-week retention. In experiment 2, intrahippocampal injections of WIN were administered to the dorsal hippocampus following each training day and rats were again probe-tested 1 week or 4 weeks later. Rats bilaterally infused with WIN at 2.5 microg and 5 microg (per side) during training spent significantly less time in the target quadrant than vehicle controls on probe trial 4 weeks later, while no difference was seen at 1-week retention. Taken together, our results showed that post-training activation of CB1 receptors in the hippocampus disrupts long-term memory consolidation but has no effect on acquisition and short-term retention. Plausible pharmacological interactions between cannabinoids and other neurotransmitter systems and associated plasticity mechanisms are discussed.
authors.affiliation: Canadian Centre for Behavioural Neuroscience, Department of Psychology and Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB, Canada T1K 3M4.
authors.forename: T T
authors.initials: TT
authors.lastname: Yim
authors.forename: N S
authors.initials: NS
authors.lastname: Hong
authors.forename: M
authors.initials: M
authors.lastname: Ejaredar
authors.forename: J E
authors.initials: JE
authors.lastname: McKenna
authors.forename: R J
authors.initials: RJ
authors.lastname: McDonald
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology; D009025:Morpholines / Q000008:administration & dosage; D009281:Naphthalenes / Q000008:administration & dosage; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone