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Disruption of CB(1) receptor signaling impairs extinction of spatial memory in mice.
Psychopharmacology (Berl). 2005 Jun; 179(4):863-72.P

Abstract

RATIONALE

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.

OBJECTIVES

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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA 23298-0613, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15619104

Citation

Varvel, S A., et al. "Disruption of CB(1) Receptor Signaling Impairs Extinction of Spatial Memory in Mice." Psychopharmacology, vol. 179, no. 4, 2005, pp. 863-72.
Varvel SA, Anum EA, Lichtman AH. Disruption of CB(1) receptor signaling impairs extinction of spatial memory in mice. Psychopharmacology (Berl). 2005;179(4):863-72.
Varvel, S. A., Anum, E. A., & Lichtman, A. H. (2005). Disruption of CB(1) receptor signaling impairs extinction of spatial memory in mice. Psychopharmacology, 179(4), 863-72.
Varvel SA, Anum EA, Lichtman AH. Disruption of CB(1) Receptor Signaling Impairs Extinction of Spatial Memory in Mice. Psychopharmacology (Berl). 2005;179(4):863-72. PubMed PMID: 15619104.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disruption of CB(1) receptor signaling impairs extinction of spatial memory in mice. AU - Varvel,S A, AU - Anum,E A, AU - Lichtman,A H, Y1 - 2004/12/24/ PY - 2004/09/03/received PY - 2004/11/07/accepted PY - 2004/12/25/pubmed PY - 2005/9/16/medline PY - 2004/12/25/entrez SP - 863 EP - 72 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 179 IS - 4 N2 - RATIONALE: 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. OBJECTIVES: 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/15619104/Disruption_of_CB_1__receptor_signaling_impairs_extinction_of_spatial_memory_in_mice_ L2 - https://dx.doi.org/10.1007/s00213-004-2121-2 DB - PRIME DP - Unbound Medicine ER -