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Novel Therapy for Nicotine Addiction in Alcohol Dependent Rats
Mona Boules, Bethany Stennett, Naveen Muhktar, Zhimin Li, Shui Cai and Elliott Richelson
Background: NT69L, a non-selective neurotensin agonist, provides a potential novel therapy for nicotine addiction in alcoholics by interacting with the common neurotransmitter circuits supporting the rewarding process for both nicotine and alcohol. Considering the behavioral effects of NT69L in attenuating nicotine self-administration in rats and alcohol consumption in mice, this study was designed to assess the effects of NT69L on nicotine self-administration in alcoholdependent rats.
Methods: Wistar rats pre-exposed to alcohol vapor or air were allowed to self-infuse nicotine (0.03 mg/kg/infusion) or saline. When the rats reached a stable level of responding, the effect of pretreatment with NT69L (1 mg/kg i.p.) on the reinforcing effect of nicotine was determined. The effect of NT69L on withdrawal signs caused by the discontinuation of nicotine and alcohol were recorded. Additionally, the effect of NT69L on dopamine and glutamate in the nucleus accumbens of rats that were co-injected with nicotine (0.5 mg/kg s.c.) and alcohol (1 g/kg i.p.) was determined with the use of in vivo microdialysis with HPLC and capillary electrophoresis.
Results: Animals self-infused nicotine at a significantly (P<0.05) higher rate compared to saline in both air and alcohol vapor exposed groups. Acute treatment with a single injection of NT69L significantly (P<0.05) reduced nicotine self-infusion in both the alcohol vapor and the air exposed groups for 5 days post-injection. NT69L also reduced the withdrawal signs associated with the discontinuation of alcohol and nicotine administration. Additionally, NT69L attenuated the alcohol- and nicotine-induced increase in dopamine and glutamate in the nucleus accumbens.
Conclusion: NT agonists may represent a potential novel therapy to treat alcohol and nicotine addiction simultaneously by modulating dopamine and glutamate.