Rationale Previous studies demonstrated that pharmacological blockade of CB1 cannabinoid receptors decreases the
extinction of conditioned fear and spatial memory in
rodents. However, the effects of CB1 cannabinoid receptor
activation in this response remain unclear.
Objectives To evaluate the effects of the cannabinoid
agonist WIN 55,212-2 (WIN) and the cannabinoid antagonist SR 147778 (SR) on the extinction of contextual fear
memory in rats 24 h or 30 days after fear conditioning.
Methods For fear conditioning, rats were placed in the
conditioning chamber for 3 min and received a 1-s electric foot
shock (1.5 mA). Retrieval testing consisted of a 3-min exposure
to the conditioning chamber and extinction training consisted of
successive 9-min exposures at 24-h intervals. Rats were also
evaluated in the open field and water maze reversal task.
Results The administration of SR (1.0 mg/kg, i.p.) and
WIN (0.25 mg/kg, i.p.) before extinction training disrupted
and facilitated, respectively, the extinction of 24 h contextual fear memory. These effects were not related to any
disturbance in memory retrieval, unconditioned freezing
expression, or locomotor activity. WIN (0.25 mg/kg, i.p.)
also facilitated the extinction of 30-day-old contextual fear
memory, while the prior administration of SR (0.2 mg/kg,
i.p.) antagonized this response. The facilitative effect of
WIN on memory extinction does not seem to be specific for
contextual fear memory because it was also observed in the
water maze reversal task.
Conclusions These results suggest cannabinoid receptor
agonists as potential drugs to treat anxiety disorders related
to the retrieval of aversive memories.
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