Evidence that mesoaccumbens dopamine and locomotor responses to nicotine in the rat are influenced by pretreatment dose and strain

Rationale: Sensitisation of the mesoaccumbens dopamine response to nicotine has been implicated in the development of nicotine dependence. This study explored the doses of nicotine that elicit the response in two strains of r ats that differ in their baseline levels of activity. Methods: Male Sprague -Dawley and Lister hooded rats were pretreated with daily subcutaneous inje ctions of (-)-nicotine for 7 days at doses ranging from 0.03 mg/kg to 0.90 mg/kg. Microdialysis studies were performed on day 9 in conscious freely mo ving rats, placed in an activity box and challenged with 0.4 mg/kg nicotine . Results: The acute administration of nicotine to drug-naive rats stimulat ed dopamine overflow in the accumbal shell but not the core. Sprague-Dawley rats, pretreated with nicotine (0.03 mg/kg/day and 0.10 mg/kg/day) showed increased basal overflow of dopamine in the accumbal core. Pretreatment wit h 0.10 mg/kg/day or 0.30 mg/kg/day, but not 0.03 mg/kg/day or 0.90 mg/kg/da y, also caused sensitisation of the response to a nicotine challenge on the test day. Sensitisation of the locomotor response to nicotine exhibited a simple dose-response relationship, with the largest sensitisation being obs erved in animals pretreated with 0.90 mg/kg/day. In Lister hooded rats. pre treatment with nicotine reduced basal dopamine overflow in the accumbal cor e and did not cause sensitisation to a subsequent challenge with nicotine. Conclusions: Sensitisation of the mesoaccumbens dopamine response to nicoti ne is influenced by pretreatment dose and the strain of rats used. It is no t related directly to the expression of sensitised locomotor responses to t he drug and, therefore, may be implicated in other psychopharmacological pr operties of the drug, including dependence.