Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats

Abstract

Rationale: The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior.

Objective: The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine.

Methods: In experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In experiment 2, rats were injected with paroxetine (2.5, 5, or 10 mg/kg), fluoxetine (5, 10, or 20 mg/kg), or vehicle during the same time frame as experiment 1, and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle.

Results: Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration.

Discussion: These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors.

Fig. 1

Mean (±SEM) body weights of male and female rats treated with vehicle, 2.5 or 10 mg/kg paroxetine (PAX), or 10 mg/kg fluoxetine (FLU) from PD 35 to PD 44. * Significant difference between vehicle- and fluoxetine-treated rats of the same sex. † Significant difference between vehicle- and 10 mg/kg paroxetine-treated rats of the same sex.

Fig. 2

Mean (±SEM) percent time spent in the open arms of the elevated plus maze. Male and female rats were treated with vehicle, 2.5 or 10 mg/kg paroxetine (PAX), or 10 mg/kg fluoxetine (FLU) from PD 35 to PD 44. * Significant difference between vehicle- and 10 mg/kg paroxetine-treated rats.

Fig. 3

Mean (±SEM) body weights of male and female rats treated with vehicle, 2.5, 5 or 10 mg/kg paroxetine (PAX), or 5, 10 or 20 mg/kg fluoxetine (FLU) from PD 35 to PD 44. *Significantly different from vehicle-treated rats of the same sex.

Fig. 4

Mean (±SEM) percent time spent in the open arms (top panels), total head dips (middle panels), and closed arm entries (bottom panels) on the elevated plus maze. Male and female rats were treated with vehicle, 2.5, 5 or 10 mg/kg paroxetine (PAX), or 5, 10 or 20 mg/kg fluoxetine (FLU) from PD 35 to PD 44. * Significant difference from vehicle-treated rats.

Fig. 5

Mean (±SEM) time spent in light compartment (top panels) and light/dark compartment transitions (bottom panels) during a 10 min test in the light/dark box. Male and female rats were treated with vehicle, 2.5, 5 or 10 mg/kg paroxetine (PAX), or 5, 10 or 20 mg/kg fluoxetine (FLU) from PD 35 to PD 44. * Significant difference from vehicle-treated rats.

Fig. 6

Mean (±SEM) startle magnitude (top panels) and startle habituation (bottom panels) on the test day. Male and female rats were treated with vehicle, 2.5, 5 or 10 mg/kg paroxetine (PAX), or 5, 10 or 20 mg/kg fluoxetine (FLU) from PD 35 to PD 44. *Significant difference from vehicle-treated rats. ^†Significant difference from vehicle-treated male rats. ^‡Significant difference from same-sex vehicle-treated rats.