l-tetrahydropalmatine reduces nicotine self-administration and reinstatement in rats

Background: The negative consequences of nicotine use are well known and documented, however, abstaining from nicotine use and achieving abstinence poses a major challenge for the majority of nicotine users trying to quit. l-Tetrahydropalmatine (l-THP), a compound extracted from the Chinese herb Corydalis, displayed utility in the treatment of cocaine and heroin addiction via reduction of drug-intake and relapse. The present study examined the effects of l-THP on abuse-related effects of nicotine. Methods: Self-administration and reinstatement testing was conducted. Rats trained to self-administer nicotine (0.03 mg/kg/injection) under a fixed-ratio 5 schedule (FR5) of reinforcement were pretreated with l-THP (3 or 5 mg/kg), varenicline (1 mg/kg), bupropion (40 mg/kg), or saline before daily 2-h sessions. Locomotor, food, and microdialysis assays were also conducted in separate rats. Results: l-THP significantly reduced nicotine self-administration (SA). l-THP's effect was more pronounced than the effect of varenicline and similar to the effect of bupropion. In reinstatement testing, animals were pretreated with the same compounds, challenged with nicotine (0.3 mg/kg, s.c.), and reintroduced to pre-extinction conditions. l-THP blocked reinstatement of nicotine seeking more effectively than either varenicline or bupropion. Locomotor data revealed that therapeutic doses of l-THP had no inhibitory effects on ambulatory ability and that l-THP (3 and 5 mg/kg) significantly blocked nicotine induced hyperactivity when administered before nicotine. In in-vivo microdialysis experiments, l-THP, varenicline, and bupropion alone elevated extracellular dopamine (DA) levels in the nucleus accumbens shell (nAcb). Conclusions: Since l-THP reduces nicotine taking and blocks relapse it could be a useful alternative to varenicline and bupropion as a treatment for nicotine addiction.