Because it was reported that diabetic rodents were resistant to the effects of several tricyclic antidepressants in various psychopharmacological models, we decided to test the hypothesis that the serotonergic dysfunction seen in diabetes might participate in this phenomenon. The ability of three serotonin-uptake blockers to reverse the performance deficit in learning induced by previous uncontrollable stress (learned-helplessness paradigm) was investigated in streptozocin-induced diabetic rats. Three weeks after induction of diabetes, rats were subjected to a session of 60 inescapable electric foot shocks and, after 48 h, to three daily sessions of two-way shuttle-box training. Three serotonin-uptake blockers were given intraperitoneally over 5 consecutive days. As with nondiabetic rats, citalopram (1 mg · kg−1 · day−1), fluoxetine (2 and 4 mg · kg−1 · day−1), and fluvoxamine (4 mg · kg 1 · day−1) reduced the number of escape failures in diabetic rats. From these data, we suggest that it is unlikely that the impaired response of diabetic rats to tricyclic antidepressants is caused by serotonergic dysfunction.

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