Chronic paroxetine infusion influences macronutrient selection in male Sprague-Dawley rats

Decreased intake and weight loss are among the side effects frequently reported with chronic selective serotonin reuptake inhibitor (SSRI) use in both humans and animals. In an earlier study, we documented that paroxetine administered for several weeks induced a weight loss of greater than 10% in some male Sprague-Dawley rats (Pharmacol. Biochem. Behav. 63 (1999) 435). As a follow-up to that work, we investigated in this study whether such treatment influenced dietary macronutrient selection. Animals were first habituated to foods containing principally either proteins, fats, or carbohydrates in a self-selection paradigm, after which they were implanted intraperitoneally with osmotic minipumps that delivered either paroxetine (7.5 mg/kg/day) or vehicle (50:50 ethanol:water) for 28 days; food intake and weight changes were documented during this period. No acute effects of the drug were apparent. By the fifth day of treatment, significant differences in weight gain between groups were observed and thereafter generally maintained for the remainder of the study, with animals receiving paroxetine showing about an 8% decrease in weight gain overall. Carbohydrate and fat intakes were significantly reduced, whereas preference was unchanged in fats and proteins and initially decreased in carbohydrates; in the latter, this pattern reversed and exceeded vehicle animals for the second half of the study. Several hypotheses are discussed with respect to specific and nonspecific effects of paroxetine on feeding and macronutrient selection.