Role of nicotine in depression through dopaminergic mechanism

Rahul Raghunath Bhalsinge, Rajbhoj Satkar, Sayan Das, Shraddha Yadav, Shah A. S., P. S. Worlikar


Background: There are interesting reports in the literature indicating relationship of smoking /nicotine and depression. Smokers use nicotine to treat depression. The objectives of present study were to evaluate the role of nicotine in depression through Dopaminergic mechanism by using haloperidol induced catalepsy model in rats and to estimate Dopamine level in brain of depressed rats after nicotine and imipramine.

Methods: Dopaminergic activity was evaluated in haloperidol induced catalepsy in rats. Levels of dopamine in normal as well as in depressed rats brain was estimated using fluorimetric method. The study treatment were administered as follows - Vehicle (s.c.), Imipramine (i.p.) - 7days, Nicotine (subcutaneous), Nicotine (inhalation) were administered in a dose of 1ml/kg,10mg/kg,0.4mg/kg,0.2mg/kg respectively.

Results: In haloperidol induced catalepsy model, vehicle treated group showed cataleptic effect starting at 1 hour and lasting for 6 hours. Nicotine administered by subcutaneous route significantly reduced cataleptic score as compared to vehicle treated group till 6 hours. Nicotine administered by inhalation route reduced cataleptic score up to 6 hours compared with that of vehicle. Catalepsy score in nicotine (inhalation) group was significantly less as compared to nicotine (subcutaneous) at all time points period except 2 hours. Isolation induced hyperactivity model was used to induce depression in rats. Dopamine levels in rats after isolation were significantly less as compared to normal rats (before isolation). After isolation, dopamine levels in imipramine treated rats were significantly higher as compared to vehicle treated group. After isolation, dopamine levels were significantly high in both groups i.e., nicotine (subcutaneous) and nicotine (inhalation). Imipramine (7 days) and single dose of nicotine (inhalation) showed comparable results with normal dopamine level i.e. before isolation rats.

Conclusions: Nicotine has increased dopaminergic activity as evident by reversal of haloperidol induced catalepsy. Dopamine level reduced in depressed rats. Dopamine brain levels were increased, when depressed rats were treated with Imipramine (i.p.), nicotine (s.c.), nicotine(inhaled). Single dose nicotine given by inhalation route has produced significant antidepressant action comparable to that of seven days’ treatment of standard antidepressant drug imipramine in rats. In rats, nicotine by both routes i.e subcutaneous and inhalational increased dopaminergic activity.


Catalepsy, Dopamine, Depression, Haloperidol induced catalepsy, Isolation induced hyperactivity, Nicotine

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