Selective breeding for high alcohol preference increases the sensitivity of the posterior VTA to the reinforcing effects of nicotine.

The rate of codependency for alcohol and nicotine is extremely high. Numerous studies have indicated that there is a common genetic association for alcoholism and nicotine dependency. The current experiments examined whether selective breeding for high alcohol preference in rats may be associated with increased sensitivity of the posterior ventral tegmental area (pVTA) to the reinforcing properties of nicotine. In addition, nicotine can directly bind to the serotonin-3 (5-HT3 ) receptor, which has been shown to mediate the reinforcing properties of other drugs of abuse within the pVTA Wistar rats were assigned to groups that were allowed to self-infuse 0, 10, 50, 100, 200, 400 or 800 µM nicotine in two-lever (active and inactive) operant chambers. P rats were allowed to self-infuse 0, 1, 10, 50 or 100 µM nicotine. Co-infusion of 5-HT3 receptor antagonists with nicotine into the pVTA was also determined. P rats self-infused nicotine at lower concentrations than required to support self-administration in Wistar rats. In addition, P rats received more self-infusions of 50 and 100 µM nicotine than Wistar rats; including a 5HT3 receptor antagonist (LY-278,584 or zacopride) with nicotine reduced responding on the active lever. Overall, the data support an association between selective breeding for high alcohol preference and increased sensitivity of the pVTA to the reinforcing properties of nicotine. In addition, the data suggest that activation of 5HT3 receptors may be required to maintain the local reinforcing actions of nicotine within the pVTA.

Nicotine exposure during adolescence enhances behavioral sensitivity to nicotine during adulthood in Wistar rats.

RATIONALE: Drug use during adolescence is associated with an increased propensity for drug dependency during adulthood. Therefore, the effects of adolescent exposure to nicotine on adult behavioral responsiveness to nicotine are of particular importance. OBJECTIVES: The objective of the current study was to determine if adolescent nicotine exposure would enhance behavioral sensitivity and development of sensitization to nicotine during adulthood. MATERIALS AND METHODS: Male Wistar rats were assigned to one of three groups that received subcutaneous (s.c.) injections of nicotine (0, 0.25, or 0.5mg/kg) in the home cage for 12 consecutive days during adolescence, PD 31-42. Starting on PD 80, distance traveled, rearing, and stereotypy were recorded in locomotor activity chambers each day for 10 days, following s.c. injections of 0, 0.25, or 0.5mg/kg nicotine. One week later, a final challenge session took place during which rats were injected with 0.5mg/kg nicotine. RESULTS: Rats exposed to nicotine during adolescence displayed a greater locomotor response to a novel environment than saline-treated rats. Adolescent nicotine treatment also resulted in context-independent sensitization to the acute locomotor activating properties of nicotine, including distance traveled and stereotypy, as measured on the first day of adulthood nicotine exposure. Adolescent nicotine-treated rats displayed increased sensitivity to repeated nicotine exposures during adulthood, compared to adolescent saline-treated rats, as measured by distance traveled, rearing, and stereotypic behaviors. Finally, rats treated with nicotine only during adolescence were more sensitive to a final nicotine challenge during adulthood than rats treated with nicotine only previously during adulthood. CONCLUSIONS: Overall, the results suggest that adolescent nicotine treatment predisposes adult rats to develop increased behavioral sensitivity to chronic nicotine treatment and to be more sensitive to the initial effects of nicotine.