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The Journal of Neuroscience, December 1, 2000, 20(23):8932-8942
Cannabinoids Reveal the Necessity of Hippocampal Neural Encoding
for Short-Term Memory in Rats
Robert E.
Hampson and
Sam A.
Deadwyler
Department of Physiology and Pharmacology and Center for
Neurobiological Investigation of Drug Abuse, Wake Forest University
School of Medicine, Winston Salem, North Carolina 27157
The memory-disruptive effects of
 9-tetrahydrocannabinol (9-THC) and the
synthetic cannabinoid WIN 55,212-2 (WIN-2) were assessed in rats
exposed to varying doses of each drug (9-THC, 0.5-2.0
mg/kg; WIN-2, 0.25-0.75 mg/kg) during performance of a delayed
nonmatch to sample (DNMS) task. Cannabinoids affected performance in a
dose × delay-dependent manner, with WIN-2 showing a potency more than
four times that of 9-THC. These effects on DNMS
performance were eliminated if the cannabinoid CB1 receptor antagonist
SR141617A (Sanofi Research Inc.) was preadministered, but doses of the
antagonist alone had no effect on performance. Simultaneous recording
from ensembles of hippocampal neurons revealed that both WIN-2 and
9-THC produced dose-dependent reductions in the
frequency (i.e.,"strength") of ensemble firing during the sample
phase of the task to the extent that performance was at risk for errors
on >70% of trials as a function of delay. This decrease in ensemble
firing in the Sample phase resulted from selective interference with
the activity of differentiated hippocampal functional cell types, which
conjunctively encoded different combinations of task events. A
reduction in ensemble firing strength did not occur in the nonmatch
phase of the task. The findings indicate that activation of CB1
receptors renders animals at risk for retention of item-specific
information in much the same manner as hippocampal removal.
Key words:
cannabinoids; memory; hippocampus; neural ensembles; encoding; dose dependence; agonists/antagonists
Copyright © 2000 Society for Neuroscience 0270-6474/00/20238932-11$05.00/0
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