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 µg/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.

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