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Role of different brain structures in the behavioural expression of WIN 55,212-2 withdrawal in mice.
Br J Pharmacol. 2004 Aug; 142(8):1309-17.BJ

Abstract

We have evaluated several responses induced by the cannabinoid agonist WIN 55,212-2 related to its addictive properties, including rewarding effects and the development of physical dependence in mice. Moreover, we have studied the specific involvement of several brain regions with high density of CB1 cannabinoid receptors, such as striatum, hippocampus, amygdala and cerebellum, in the behavioural expression of SR 141716A-precipitated WIN 55,212-2 withdrawal. The systemic administration of the CB1 receptor antagonist SR 141716A (10 mg kg(-1), s.c.) precipitated behavioural signs of withdrawal in mice chronically treated with WIN 55,212-2 (1 and 2 mg kg(-1), intraperitoneal (i.p.)), revealing the development of physical dependence. The microinjection of SR 141716A (1.5 and 3 micrograms) into the cerebellum induced severe manifestations of abstinence in mice dependent on WIN 55,212-2 (1 mg kg(-1), i.p.). Out of 10 signs evaluated, seven were statistically significant: wet dog shakes, body tremor, paw tremor, piloerection, mastication, genital licks and sniffing. When the cannabinoid antagonist was administered into the hippocampus and the amygdala, a moderate but significant withdrawal syndrome was also observed. However, no signs of abstinence were induced when SR 141716A was microinjected into the striatum. WIN 55,212-2 produced rewarding effects in the place-conditioning paradigm in mice pre-exposed to a priming injection of the drug. These results show a reliable behavioural model to reveal rewarding effects and physical dependence induced by the repeated administration of WIN 55,212-2 in mice. The cerebellum and to a lesser extent the hippocampus and the amygdala participate in the behavioural expression of cannabinoid withdrawal.

Authors+Show Affiliations

Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, C/ Dr. Aiguader, 80, 08003 Barcelona, Spain.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15265804

Citation

Castañé, Anna, et al. "Role of Different Brain Structures in the Behavioural Expression of WIN 55,212-2 Withdrawal in Mice." British Journal of Pharmacology, vol. 142, no. 8, 2004, pp. 1309-17.
Castañé A, Maldonado R, Valverde O. Role of different brain structures in the behavioural expression of WIN 55,212-2 withdrawal in mice. Br J Pharmacol. 2004;142(8):1309-17.
Castañé, A., Maldonado, R., & Valverde, O. (2004). Role of different brain structures in the behavioural expression of WIN 55,212-2 withdrawal in mice. British Journal of Pharmacology, 142(8), 1309-17.
Castañé A, Maldonado R, Valverde O. Role of Different Brain Structures in the Behavioural Expression of WIN 55,212-2 Withdrawal in Mice. Br J Pharmacol. 2004;142(8):1309-17. PubMed PMID: 15265804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of different brain structures in the behavioural expression of WIN 55,212-2 withdrawal in mice. AU - Castañé,Anna, AU - Maldonado,Rafael, AU - Valverde,Olga, Y1 - 2004/07/20/ PY - 2004/7/22/pubmed PY - 2005/1/27/medline PY - 2004/7/22/entrez SP - 1309 EP - 17 JF - British journal of pharmacology JO - Br J Pharmacol VL - 142 IS - 8 N2 - We have evaluated several responses induced by the cannabinoid agonist WIN 55,212-2 related to its addictive properties, including rewarding effects and the development of physical dependence in mice. Moreover, we have studied the specific involvement of several brain regions with high density of CB1 cannabinoid receptors, such as striatum, hippocampus, amygdala and cerebellum, in the behavioural expression of SR 141716A-precipitated WIN 55,212-2 withdrawal. The systemic administration of the CB1 receptor antagonist SR 141716A (10 mg kg(-1), s.c.) precipitated behavioural signs of withdrawal in mice chronically treated with WIN 55,212-2 (1 and 2 mg kg(-1), intraperitoneal (i.p.)), revealing the development of physical dependence. The microinjection of SR 141716A (1.5 and 3 micrograms) into the cerebellum induced severe manifestations of abstinence in mice dependent on WIN 55,212-2 (1 mg kg(-1), i.p.). Out of 10 signs evaluated, seven were statistically significant: wet dog shakes, body tremor, paw tremor, piloerection, mastication, genital licks and sniffing. When the cannabinoid antagonist was administered into the hippocampus and the amygdala, a moderate but significant withdrawal syndrome was also observed. However, no signs of abstinence were induced when SR 141716A was microinjected into the striatum. WIN 55,212-2 produced rewarding effects in the place-conditioning paradigm in mice pre-exposed to a priming injection of the drug. These results show a reliable behavioural model to reveal rewarding effects and physical dependence induced by the repeated administration of WIN 55,212-2 in mice. The cerebellum and to a lesser extent the hippocampus and the amygdala participate in the behavioural expression of cannabinoid withdrawal. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/15265804/Role_of_different_brain_structures_in_the_behavioural_expression_of_WIN_55212_2_withdrawal_in_mice_ DB - PRIME DP - Unbound Medicine ER -