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


METHODS
HU210 (100 microg 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.


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 CB(1) 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
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.
Robinson
L
L
Department of Biomedical Sciences, Institute for Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
Goonawardena
A V
AV
Pertwee
R G
RG
Hampson
R E
RE
Riedel
G
G
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002186:Cannabinoids / Q000633:toxicity*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000633:toxicity; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects; D000077285:Rimonabant; D013028:Space Perception / Q000187:drug effects*
D002186:Cannabinoids; D009025:Morpholines; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol; C062018:HU 211; D000077285:Rimonabant; C109925:AM 281