Rapid tolerance to Delta(9)-tetrahydrocannabinol and cross-tolerance between ethanol and Delta(9)-tetrahydrocannabinol in mice

Motor incoordination in the rota-rod test was used to assess the developmen t of rapid tolerance to Delta (9)-tetrahydrocannabinol and rapid cross-tole rance between ethanol and Delta (9)-tetrahydrocannabinol in mice: Further, the influence of the cannabinoid receptor antagonist SR 141716A (N-(piperid in-1-yl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide) on the mot or impairment induced by both drugs was examined. Mice were injected on day 1 with equipotent doses of Delta (9)-tetrahydrocannabinol (28 mg/kg, i.p.) and ethanol (2.25 g/kg, i.p.) and tested at 30, 60 and 90 min after the in jections. On day 2, control groups received ethanol or Delta (9)-tetrahydro cannabinol, some groups received the same treatment as the day before, whil e the remaining groups switched the treatment. All groups were tested to ev aluate tolerance. The development of rapid tolerance to Delta (9)-tetrahydr ocannabinol was observed and pretreatment with ethanol resulted in rapid cr oss-tolerance to Delta (9)-tetrahydrocannabinol. SR 141716A (2 mg/kg, i.p.) failed to block the development of rapid tolerance to both drugs, ethanol and Delta (9)-tetrahydrocannabinol. These results suggest that Delta (9)-te trahydrocannabinol, similarly to ethanol, can induce rapid tolerance to mot or incoordination in mice. They also support the use of the 2-day protocol as an effective procedure to reduce the length of drug exposure necessary t o induce tolerance. (C) 2001 Elsevier Science B.V. All rights reserved.