The CB1 cannabinoid receptor in brain mediates the behavioral effects of sedation, antinociception, short-term memory loss and muddled thinking. In animal studies, tobacco smoke as well as nicotine induce the activity of several enzymes, including CYP2E1, CYP2A1/2A2 and CYP2B1/2B2, in the brain, but whether this effect is clinically significant is unknown. This study examined the effects of prior exposure to tobacco smoke as well as nicotine on the behavioral effects of cannabinoid and aminoalkylindole agonists (delta-9-tetrahydrocannabinol, CP55244 and WIN55212-2) in male mice and rats. METHODS: Mice (male A/J strain, 5 weeks old ;N=70) and male Sprague-Dawley rats, 5 weeks old (N = 70) were exposed to tobacoo smoke in metabolic cages for 45 days. In addition, separate groups of animals (N=30) were injected daily with nicotine (the psychoactive component in tobacco, 1 mg/kg, i.p.) or vehicle for 45 days On test day, animals were injected with delta-9- tetrahydrocannabinol, CP55244 and WIN55212-2 (0.5, 2.0, or 5.0 mg/kg, i.p.) or vehicle The animals were evaluated regarding their performance in: 1. Open field method to test spontaneous locomotor activity. 2. Morris water maze test . 3. Radial-arm maze test. 4. Rota-rod test 5. Hot-plate and tail-Flick tests 6. Social interaction test. RESULTS: Chronic exposure to tobacco smoke and nicotine pretreatment
attenuated some of the behavioral effects induced by delta-9-tetrahydrocannabinol, CP55244 and WIN55212-2, which can be summarized as follows: (a) prior exposure to tobacoo smoke and nicotine attenuated the effect of the tested drugs on locomotor acvtivity, sedation but with no significant effect on social interaction. (b) prior exposure to tobacoo smoke and nicotine attenuated the effect of the tested drugs on pain and short-term memory. (c) Tobacoo smoke was somewhat more effective than nicotine in these tests, may be due to the presence of other active constituents in tobacoo smoke.
CONCLUSIONS: The ability of chronic tobacoo smoke and nicotine prior exposure to produce long-lasting changes that alter the effects of acute drug administration suggests that chronic tobacoo smoke and nicotine may induce neuroplastic changes that influence the subsequent response to cannabinoid drug exposure.