Peripheral and intra-dorsolateral striatum injections of the cannabinoid receptor agonist WIN 55,212-2 impair consolidation of stimulus-response memory.
The endocannabinoid system plays a major role in modulating memory. In the present study, we examined whether cannabinoid agonists influence the consolidation of stimulus-response/habit memory, a form of memory dependent upon the dorsolateral striatum (DLS). In Experiment 1, rats were trained in a cued platform water maze task in which animals were released from different start points and in order to escape had to find a cued platform which was moved to various spatial locations across trials. Immediately following training, rats received an i.p. injection of the cannabinoid receptor agonist WIN 55,212-2 (1 or 3mg/kg) or a vehicle solution. In Experiment 2, rats were trained in a forced-response version of the water plus-maze task in which a consistent body-turn response was reinforced across trials. Immediately following training, rats received an i.p. injection of WIN 55,212-2 (3 mg/kg) or vehicle. In Experiment 3, rats were trained in the cued platform task and after training received bilateral intra-DLS WIN 55,212-2 (100 ng/.5 μL or 200 ng/.5 μL) or vehicle. In Experiments 1-3, the higher doses of WIN 55,212-2 were associated with significant memory impairments, relative to vehicle-treated controls. The results indicate that peripheral or intra-DLS administration of a cannabinoid receptor agonist impairs consolidation of DLS-dependent memory. The findings are discussed within the context of previous research encompassing cannabinoids and DLS-dependent learning and memory processes, and the possibility that cannabinoids may be used to treat some habit-like human psychopathologies (e.g. posttraumatic stress disorder) is considered.
Department of Psychology, Institute for Neuroscience, Texas A&M University, United States.
J
J
Goodman
Department of Psychology, Institute for Neuroscience, Texas A&M University, United States. Electronic address: markpackard@tamu.edu.
M G
MG
Packard
D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage*; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D009025:Morpholines / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000008:administration & dosage*; D017072:Neostriatum / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology
D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
cannabinoid; caudate-putamen; dorsolateral striatum; habit memory; marijuana; post-traumatic stress disorder