The synthetic cannabinoid HU210 induces spatial memory deficits and suppresses hippocampal firing rate in rats

Abstract

Background and purpose: Previous work implied that the hippocampal cannabinoid system was particularly important in some forms of learning, but direct evidence for this hypothesis is scarce. We therefore assessed the effects of the synthetic cannabinoid HU210 on memory and hippocampal activity. Experimental approach: HU210 (100 μg kg^‐1) was administered intraperitoneally to rats under three experimental conditions. One group of animals were pre‐trained in spatial working memory using a delayed‐matching‐to‐position task and effects of HU210 were assessed in a within‐subject design. In another, rats were injected before acquisition learning of a spatial reference memory task with constant platform location. Finally, a separate group of animals was implanted with electrode bundles in CA1 and CA3 and single unit responses were isolated, before and after HU210 treatment. Key results: HU210 treatment had no effect on working or short‐term memory. Relative to its control Tween 80, deficits in acquisition of a reference memory version of the water maze were obtained, along with drug‐related effects on anxiety, motor activity and spatial learning. Deficits were not reversed by the CB₁ receptor antagonists SR141716A (3 mg kg^‐1) or AM281 (1.5 mg kg^‐1). Single unit recordings from principal neurons in hippocampal CA3 and CA1 confirmed HU210‐induced attenuation of the overall firing activity lowering both the number of complex spikes fired and the occurrence of bursts. Conclusions and implications: These data provide the first direct evidence that the underlying mechanism for the spatial memory deficits induced by HU210 in rats is the accompanying abnormality in hippocampal cell firing. British Journal of Pharmacology (2007) 151, 688–700; doi:10.1038/sj.bjp.0707273