کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2493616 | 1556651 | 2011 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Pharmacological elevation of anandamide impairs short-term memory by altering the neurophysiology in the hippocampus Pharmacological elevation of anandamide impairs short-term memory by altering the neurophysiology in the hippocampus](/preview/png/2493616.png)
In rodents, many exogenous cannabinoid agonists including Δ9-THC and WIN55,212-2 (WIN-2) have been shown to impair short-term memory (STM) by inhibition of hippocampal neuronal assemblies. However, the mechanisms by which endocannabinoids such as anandamide and 2-arachidonyl glycerol (2-AG) modulate STM processes are not well understood. Here the effects of anandamide on performance of a Delayed-Non-Match-to-Sample (DNMS) task (i.e. STM task) and concomitant hippocampal ensemble activity were assessed following administration of either URB597 (0.3, 3.0 mg/kg), an inhibitor of the Fatty Acid Amide Hydrolase (FAAH), AM404 (1.5, 10.0 mg/kg), a putative anandamide uptake/FAAH inhibitor, or R-methanandamide (3.0, 10.0 mg/kg), a stable analog of anandamide. Principal cells from hippocampal CA3/CA1 were recorded extracellularly by multi-electrode arrays in Long-Evans rats during DNMS task (1–30 s delays) performance and tracked throughout drug administration and recovery. Both R-methanandamide and URB597 caused dose- and delay-dependent deficits in DNMS performance with suppression of hippocampal ensemble activity during the encoding (sample) phase. R-methanandamide-induced effects were not reversed by capsaicin excluding a contribution of TRPV-1 receptors. AM404 produced subtle deficits at longer delay intervals but did not alter hippocampal neuronal activity during task-specific events. Collectively, these data indicate that endocannabinoid levels affect performance in a STM task and their pharmacological elevation beyond normal concentrations is detrimental also for the underlying physiological responses. They also highlight a specific window of memory processing, i.e. encoding, which is sensitive to cannabinoid modulation.
► R-methanandamide and URB597 produce dose- and delay-dependent memory impairments.
► R-methanandamide-induced STM deficits are not reversed by TRPV-1 receptor antagonist.
► URB597 and R-methanandamide disrupt hippocampal ensemble firing during ‘encoding’.
► Level of ‘anandamide’ modulates encoding of a ‘short-term memory’ task.
► Low ‘endocannabinoid’ tone enables strong encoding.
Journal: Neuropharmacology - Volume 61, Issues 5–6, October–November 2011, Pages 1016–1025