Chronic DMI reduces thresholds for brain stimulation reward in the rat.

The authors sought a demonstration of the validity of brain stimulation reward (BSR) models of depression. It was predicted that chronic, but not acute antidepressant treatment would enhance BSR responding. Rats with medial forebrain bundle electrodes were separated into 4 groups that received either saline or desmethylimipramine at 5, 10, or 20 mg/kg daily. A rate-free, threshold measure that has not previously been employed in studies of BSR and antidepressants was used. BSR thresholds were monitored every 3rd day over a 9-day baseline period and an 18-day drug treatment period, and after 12 days of drug withdrawal. Groups did not differ from one another till the 15th and 18th day of drug treatment. The greatest effects were seen in the 10 and 20 mg groups. The 20 mg group returned to baseline after drug withdrawal, but the 10 mg group did not. The absolute size of the effect was considered to be small, leading the authors to speculate that antidepressants act on homeostatic mechanisms that stabilize BSR substrates, only indirectly enhancing transmission of the reward signal.