Feeding and reward interactions from chronic paroxetine treatment

The self-stimulation paradigm was used to evaluate threshold changes following acute and chronic administration of the selective serotonergic reuptake inhibitor paroxetine; stimulation sites were located in medial forebrain bundle structures. Rats received daily systemic injections of one of three doses of paroxetine (2.5, 5, or 7.5 mg/kg), either with or without stimulation, while the last group received the same number of vehicle injections with stimulation. Frequency thresholds were collected over a period of 6 h on day 1 (acute phase); no marked difference in the values were observed over this time span. Thereafter, the animals were tested every third day (chronic phase), for a total of 11 sessions or roughly 31 days. Commencing around day 10 of the drug treatment, the higher dose of paroxetine produced a significant and persistent facilitation in self-stimulation thresholds, mimicking the delay in clinical response in humans that is well documented. We also monitored on a daily basis the animals' weights and food intake. A large difference in the percent efficiency of food utilization, measured by calculating the ratio of weight change to food intake, was observed between the animals receiving stimulation and those that were not, exclusive to the higher dose of paroxetine. The percent efficiency of food utilization remained low in the animals only receiving the drug treatment, whereas they returned to baseline levels and above in subjects receiving both paroxetine and stimulation. Two findings emerge from these data: 1) the paradigm appears to model the human response to this class of antidepressants, and 2) rewarding stimulation seems to counteract the drug-induced weight loss.