Disruption of CB(1) receptor signaling impairs extinction of spatial memory in mice.
BACKGROUND
A growing body of in vitro and in vivo evidence indicates that a central endocannabinoid system, consisting of CB(1) receptors and endogenous cannabinoids, modulates specific aspects of mnemonic processes. Previous research has demonstrated that either permanent or drug-induced disruption of CB(1) receptor signaling interferes with the extinction of a conditioned fear response.


OBJECTIVE
In the present study, we evaluated whether the endocannabinoid system also plays a role in extinguishing learned escape behavior in a Morris water maze task.


METHODS
CB(1) (-/-) mice and mice repeatedly treated with 3 mg/kg of the CB(1) receptor antagonist SR 141716 (Rimonabant) were trained to locate a hidden platform in the Morris water maze. Following acquisition, the platform was removed and subjects were assigned to either a massed (i.e., five consecutive sessions consisting of four 2-min trials/session) or a spaced (a single, 1-min trial every 2-4 weeks) extinction protocol.


RESULTS
Strikingly, both 3 mg/kg SR 141716-treated mice and CB(1) (-/-) mice continued to return to the target location across all five trials in the spaced extinction procedure, while the control mice underwent extinction by the third or fourth trial. In contrast, both the 3-mg/kg SR 141716-treated and CB(1) (-/-) mice exhibited extinction in the massed extinction trial procedure.


CONCLUSIONS
These findings indicate that disruption of CB(1) receptor signaling impairs extinction processes in the Morris water maze, thus lending further support to the hypothesis that the endocannabinoid system plays an integral role in the suppression of non-reinforced learned behaviors.
Varvel
S A
SA
Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA 23298-0613, USA.
Anum
E A
EA
Lichtman
A H
AH
D000818:Animals; D005108:Extinction, Psychological / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects*; D000077285:Rimonabant; D015398:Signal Transduction / Q000187:drug effects*; D013028:Space Perception / Q000187:drug effects*; D013550:Swimming / Q000523:psychology
D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant