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Acute administration of the CB1 cannabinoid receptor antagonist SR 141716A induces anxiety-like responses in the rat

Navarro, Miguel1,4; Hernández, Elena1; Muñoz, Raúl M.2; del Arco, Ignacio1,2; Villanúa, María Angeles2; Carrera, M Rocio A.3; Rodríguez de Fonseca, Fernando1

Neuropharmacology and Neurotoxicology

ANIMAL models have revealed that psychoactive cannabinoids induce both anxiolytic and anxiety-like reactions which are dose- and context-dependent. In the present study we examined the acute actions of the CB1 cannabinoid receptor antagonist SR 141716A in both the defensive withdrawal test and the elevated plus-maze in rats. Acute administration of SR 141716A (0.1, 1 and 3 mg kg−1) induced defensive responses in both anxiety tests, at a dose of 3 mg kg−1. This dose had no effect on horizontal locomotor activity and did not activate the hypothalamus–pituitary–adrenal axis, although several cannabinoid withdrawal-like behavioural symptoms were observed. These results demonstrate that blockade of the endogenous cannabinoid tone might induce anxiety-like responses in rats.

1Departamento de Psicobiología, Facultad de Psicología Instituto Complutense de Drogodependencias

2Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, 28223-Madrid, Spain

3Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California, USA

4Corresponding Author: Miguel Navarro.

ACKNOWLEDGEMENTS: This work has been supported by Comisión Interministerial de Ciencia y Tecnología (CICYT, grant SAF-94/0465)). The authors thank the expert assistance of Leticia Escuredo, Olivia Maestre and Yolanda Martin. They acknowledge Sanofi Recherche for providing SR 141716A. Dr. F.R.F. is a research fellow of the Fundución Jaime del Amo, Universidad Complutense de Madrid.

Received 27 September 1996; accepted 17 October 1996

© Lippincott-Raven Publishers.