Diminished conditioned responding to the nicotine stimulus by antidepressant drugs with differing specificity for the serotonin and norepinephrine transporter.

People diagnosed with depression also tend to have a co-morbid nicotine addiction. Thus, there is interest in whether medications used to treat depression alter the effects of nicotine. This study assessed whether the antidepressant drugs citalopram, imipramine, and reboxetine, with differing specificity for the serotonin and norepinephrine transporter, altered responding controlled by the conditional stimulus (CS) effects of nicotine. Rats received intermixed 20-min nicotine (0.4 mg base/kg, SC) and saline sessions. On nicotine sessions, rats had intermittent access to sucrose; no sucrose was available on saline sessions. After discrimination performance stabilized and a nicotine generalization curve (0.025-0.4 mg/kg) was established, the antidepressant drugs were assessed. In these tests, rats were pretreated with citalopram (1-17 mg/kg), imipramine (1-17 mg/kg), or reboxetine (1-30 mg/kg) before the training dose of nicotine and placement in a chamber for a 4-min extinction test. At the higher doses, all three antidepressant drugs blocked responding evoked by the nicotine CS and decreased nicotine-induced hyperactivity. When these higher doses of citalopram, imipramine, and reboxetine were tested alone (no nicotine), they decreased chamber activity and/or dipper entries. Nevertheless, all three drugs produced partial or complete blockade of the CS effects of nicotine at doses that produced no effect on dipper entries or chamber entries. This finding suggests that both neurotransmitters play a role in the CS effects of nicotine and that modifications in these systems by antidepressants may be clinically relevant.