The lesion of serotonergic neurons does not prevent antidepressant-induced reversal of escape failures produced by inescapable shocks in rats.
The present study was aimed at testing the hypothesis (based mainly on biochemical evidence) of the implication of brain serotonergic neurons in the induction of learned helplessness (escape deficit) and its reversal by antidepressants in rats. After desipramine (25 mg/kg IP)-pretreatment rats were either sham-operated or infused with 5,7-dihydroxytryptamine (5,7-DHT, 3 micrograms of free base in 0.4 microliter saline containing 0.02% ascorbic acid) into the midbrain raphe area. Three weeks later, experimental animals were exposed to 60 randomized inescapable shocks (0.8 mA; 15 sec duration), control rats being not shocked, and 48 hr later, they were subjected to daily shuttle-box sessions (30 trials/day; ITI = 30 sec) on 3 consecutive days in order to assess escape deficits. After inescapable shock pretreatment separate groups of rats were given twice daily injections of clomipramine (total daily dose: 32 mg/kg), desipramine (24 mg/kg), imipramine (32 mg/kg), nialamide (32 mg/kg) or saline. After behavioral testing, animals were sacrificed, and tryptophan hydroxylase activity was assayed in the cerebral cortex, the hippocampus and the striatum. We found that damage to serotonergic neurons associated with a 70% loss of tryptophan hydroxylase activity altered neither escape deficits produced by prior exposure to inescapable shock, nor the ability of either antidepressant studied to reverse escape failures in the shuttle-box paradigm. These findings cast some doubts on the hypothesized crucial role of serotonergic neurons in helpless behavior and its reversal by antidepressants.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002997:Clomipramine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D006380:Helplessness, Learned; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009526:Nialamide / Q000494:pharmacology; D011903:Raphe Nuclei / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*
D000928:Antidepressive Agents; D012701:Serotonin; D002997:Clomipramine; D007099:Imipramine; D009526:Nialamide; D003891:Desipramine