The effect of subchronic fluoxetine treatment on learning and memory in adolescent rats

Selective serotonin re-uptake inhibitors are increasingly used for the treatment of adolescents with behavioural disorders. However, the effect of this class of drugs during this sensitive period of brain development has not been extensively investigated. In this study we examine the effect of subchronic treatment with the selective serotonin re-uptake inhibitor, fluoxetine (10 mg/kg/day, i.p.) throughout adolescence (postnatal day 28–60) on learning and memory in the rat. Learning and memory were assessed at two time points: during adolescence, while the animals were being treated with fluoxetine and in young adulthood, 40 days after the termination of fluoxetine treatment. Fluoxetine treated rats were compared to a saline injected control group with respect to spatial navigation in the water maze, object recognition and object-in-place recognition memory. Additionally open field behaviour was examined. In adolescent rats fluoxetine treatment impaired water-maze probe trial performance and object recognition at intertrial intervals of 15 and 60 min, while leaving object-in-place recognition memory unaffected. In the open field the fluoxetine treated animals displayed reduced exploratory activity and higher levels of anxiety. Training the animals to a new platform position in young adulthood showed that the rats that had been treated with fluoxetine during adolescence were significantly slower to acquire this new spatial information. Adolescent fluoxetine treatment had no effect on cell proliferation in dorsal dentate gyrus and subgranular zone in young adulthood. This calls for further studies examining the long-term effects of this class of antidepressants on adolescent brain development and behaviour.

► Subchronic SSRI treatment of adolescent rats caused.
► Subtle deficits in water-maze learning and memory.
► Reduced exploratory activity and increased anxiety like behaviour in the open field.
► 40 days after seponation: impaired reversal learning in the water-maze, but no deficits in adult hippocampal cytogenesis.
► This calls for further studies of the effects of adolescent SSRI treatment.