Effects of the serotonin uptake inhibitor clomipramine in assays of pain‐depressed and pain‐stimulated behavior in rats

Noxious stimuli can produce pain‐related stimulation of some behaviors (e.g. withdrawal responses) and depression of other behaviors (e.g. feeding, locomotion, responding maintained by many types of positive reinforcement). Serotonin uptake inhibitors are used clinically to treat depression and to manage some types of pain. This study examined effects of the tricylclic antidepressant and serotonin uptake inhibitor clomipramine in complementary assays of pain‐stimulated and pain‐depressed behavior in rats. Intraperitoneal injection of dilute lactic acid (1.8% in a volume of 1ml/kg) was used as a noxious stimulus to stimulate a stretching response and to depress intracranial self‐stimulation (ICSS) of the median forebrain bundle. Clomipramine (3.2–32 mg/kg, i.p.) dose dependently blocked acid‐stimulated stretching but failed to block acid‐induced depression of ICSS. In the absence of the noxious stimulus, clomipramine did not alter ICSS. These results suggest that acute serotonin uptake inhibition does not prevent behavioral depressant effects associated with acute pain.