Role of different brain structures in the behavioural expression of WIN 55,212‐2 withdrawal in mice

Role of different brain structures in the behavioural expression of WIN 55,212‐2 withdrawal in... 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 μg) 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. British Journal of Pharmacology (2004) 142, 1309–1317. doi:10.1038/sj.bjp.0705882 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Role of different brain structures in the behavioural expression of WIN 55,212‐2 withdrawal in mice

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Publisher
Wiley
Copyright
2004 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
D.O.I.
10.1038/sj.bjp.0705882
Publisher site
See Article on Publisher Site

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 μg) 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. British Journal of Pharmacology (2004) 142, 1309–1317. doi:10.1038/sj.bjp.0705882

Journal

British Journal of PharmacologyWiley

Published: Aug 1, 2004

References

  • The effects of cannabinoids on the brain
    AMERI, AMERI
  • Cannabinoid withdrawal syndrome is reduced in double mu and delta opioid receptor knockout mice
    CASTAÑÉ, CASTAÑÉ; ROBLEDO, ROBLEDO; MATIFAS, MATIFAS; KIEFFER, KIEFFER; MALDONADO, MALDONADO
  • Spontaneous network activity of cerebellar granule neurons: impairment by in vivo chronic cannabinoid administration
    GHOZLAND, GHOZLAND; AGUADO, AGUADO; ESPINOSA‐PARRILLA, ESPINOSA‐PARRILLA; SORIANO, SORIANO; MALDONADO, MALDONADO
  • Inhibition of the amygdala and hippocampal calcium/calmodulin‐dependent protein kinase II attenuates the dependence and relapse to morphine differently in rats
    LU, LU; ZENG, ZENG; LIU, LIU; CENG, CENG
  • Endogenous cannabinoids as an aversive or counter‐rewarding system in the rat
    SAÑUDO‐PEÑA, SAÑUDO‐PEÑA; TSOU, TSOU; DELAY, DELAY; HOHMAN, HOHMAN; FORCE, FORCE; WALKER, WALKER
  • Cannabinoid withdrawal is dependent upon PKA activation in the cerebellum
    TZAVARA, TZAVARA; VALJENT, VALJENT; FIRMO, FIRMO; MAS, MAS; BESLOT, BESLOT; DEFER, DEFER; ROQUES, ROQUES; HANOUNE, HANOUNE; MALDONADO, MALDONADO

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