The effects of long-term administration of antidepressant drugs on intracranial self-stimulation responding in rats.

A discrimination procedure employing a two hole nose-poke technique was used to evaluate the effects of chronic administration of desipramine, amitriptyline, bupropion, nomifensine and zimelidine on intracranial self-stimulation (ICSS). Analysis of ICSS as a function of descending and ascending current presentation revealed that long-term exposure to desipramine significantly facilitated rates of responding from the medial forebrain bundle, and resulted in a shift to the left of the rate-intensity functions. The use of a discrimination paradigm allowed for the assessment of incorrect responses which proved to be a sensitive measure of the motor activating properties associated with electrical brain stimulation. These data indicated that the positive reinforcing effects of desipramine were not accompanied by concomitant increases in motor arousal. No changes in ICSS responding were evident after long-term treatment with amitriptyline, or the atypical antidepressants, bupropion, nomifensine and zimelidine. The implications of these findings were discussed in terms of the effects of these drugs on reward processes and the role of dopamine in the therapeutic efficacy of antidepressant drugs.