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Effects of SR141716 and WIN 55,212-2 on tolerance to ethanol in rats using the acute and rapid procedures

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Abstract

Rationale

Our previous findings have shown rapid cross-tolerance between ethanol and Δ9-tetrahydrocannabinol and that intraperitoneal (i.p.) injection of cannabinoid receptor type 1 (CB1R) antagonist SR141716 (SR) does not interfere with tolerance to either of these drugs in mice.

Objectives

This study investigates the effects of SR, alone or in combination with the CB receptor agonist WIN 55,212-2 (WIN), on the development of acute and rapid tolerance to the incoordinating effect of ethanol in rats.

Materials and methods

Male Wistar rats received SR, through i.p. (0.5–2.0 mg/kg) or intracerebroventricular (i.c.v.) injections (0.5–4.0 μg), alone or together with WIN (1.0 μg, i.c.v.), in combination with ethanol (2.7 g/kg, i.p.). Another group received WIN (1.0 μg, i.c.v.) in combination with ethanol (2.3 g/kg), and the rats were tested for motor coordination. Rapid tolerance was assessed 24 h later by administering ethanol to all animals and retesting them under the same dose regimen. Acute tolerance was evaluated for 75 min after ethanol (3.0 g/kg, i.p.) in animals treated with SR or WIN (i.c.v.).

Results

The reduced motor impairment on day 2 (i.e., rapid tolerance) was blocked by SR (i.p. and i.c.v.). WIN (1.0 μg, i.c.v.) facilitated rapid tolerance and also prevented the blockade of rapid tolerance by SR (1.0 μg, i.c.v.). In the acute tolerance procedure, SR did not affect the motor incoordination induced by ethanol.

Conclusions

The results suggest that the endocannabinoid system may contribute to the development of rapid tolerance to ethanol.

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Acknowledgments

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; Grant 472829/2003-3) and the Fundação de Amparo a Pesquisa de Santa Catarina (FAPESC; Grant 4705/2004-8). J.I.L. received a scholarship from CAPES, Brazil. G.S.M. and R.N.T. are research fellows of CNPq, Brazil.

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  1. Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário Trindade, CCB, 88049-900, Florianopolis, SC, Brazil

    Jose Inácio Lemos, Reinaldo Naoto Takahashi & Gina Struffaldi Morato

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  1. Jose Inácio Lemos
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  2. Reinaldo Naoto Takahashi
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Correspondence to Gina Struffaldi Morato.

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Lemos, J.I., Takahashi, R.N. & Morato, G.S. Effects of SR141716 and WIN 55,212-2 on tolerance to ethanol in rats using the acute and rapid procedures. Psychopharmacology 194, 139–149 (2007). https://doi.org/10.1007/s00213-007-0804-1

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