Prolonged cannabinoid treatment results in spatial working memory deficits and impaired long-term potentiation in the CA1 region of the hippocampus in vivo.
Adult male Long-Evans rats were administered the potent cannabinoid 1 receptor agonist HU-210 (100 microg/kg, i.p.) for 15 days continuously and their performance on a matching-to-place version of the Morris water maze was subsequently evaluated. Overall, experimental animals performed significantly worse initially on the reference memory component of this task, but their performance improved over 5 days until it was indistinguishable from that of control animals. Animals given HU-210 did not exhibit working memory impairments at short intertrial delays (30 s); however, significant impairments were observed in learning performance with longer intertrial delays (300 s). In vivo electrophysiological analyses revealed that long-term potentiation in the CA1 region of the hippocampus was significantly impaired following the administration of HU-210 for 15 days. These results indicate that long-term cannabinoid exposure can produce marked deficits in reference and working memory performance, and also impair hippocampal synaptic plasticity in vivo.
Hill
Matthew N
MN
Department of Psychology and the Brain Research Centre, 2136 West Mall, University of British Columbia, Vancouver, BC, Canada V6T 1Z4.
Froc
David J
DJ
Fox
Christopher J
CJ
Gorzalka
Boris B
BB
Christie
Brian R
BR
D000818:Animals; D001522:Behavior, Animal; D002186:Cannabinoids / Q000009:adverse effects / Q000494:pharmacology*; D013759:Dronabinol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004594:Electrophysiology / Q000379:methods; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced*; D008570:Memory, Short-Term / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D013995:Time; D013997:Time Factors
D002186:Cannabinoids; D013759:Dronabinol; C062018:HU 211