Abstract

Pre-clinical and clinical evidence suggests that the antidepressant efficacy of the selective serotonin reuptake inhibitor escitalopram can be enhanced by the dopamine and serotonin partial agonist aripiprazole. Given the range of possible neurochemical interactions between these drugs, the current study investigated whether aripiprazole alters the hedonic and psychomotor effects of escitalopram. Male Sprague Dawley rats ( n=116) received 10 mg/kg/day escitalopram (subcutaneous), 2 mg/kg/day aripiprazole (subcutaneous), or combined aripiprazole + escitalopram, and were tested for consumption of incentive nutritional stimuli (high-fructose corn syrup and chow), stereotypy and locomotor activity. At the conclusion of behavioral testing, mRNAs of two genes involved in reward processes were quantified: hypothalamic pro-opiomelanocortin and hippocampal brain-derived neurotrophic factor. Escitalopram produced a selective, but temporary, decrease in high fructose corn syrup consumption that was not altered by aripiprazole co-administration. Escitalopram had no significant effect on locomotion, but aripiprazole co-administration produced a persistent increase in stereotypy. Both brain-derived neurotrophic factor and pro-opiomelanocortin mRNA levels were lower in the aripiprazole + escitalopram group relative to the escitalopram group. Taken together, these results suggest that aripiprazole may enhance the antidepressant efficacy of escitalopram through improvement of psychomotor functions.

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