ANTIDEPRESSANT TREATMENT IN HELPLESS RATS - EFFECT ON THE ELECTROPHYSIOLOGICAL ACTIVITY OF RAPHE DORSALIS SEROTONERGIC NEURONS

Chronic treatment with antidepressants renders serotonergic neuronal f iring less sensitive to the inhibitory effect of serotonin (5-HT) reup take blockers in the rat, and this has been considered as a major corr elate of the therapeutic action of these drugs. We investigated whethe r the same mechanisms could be evidenced in an experimental model of d epression, the learned helplessness paradigm. Rats rendered helpless b y a single session of inescapable electrical footshocks exhibit, for s everal days, depression-like behavioural deficits which can be reverse d by sub-chronic, but not acute, treatment with antidepressants. Recor ding of serotonergic neurons in the dorsal raphe nucleus revealed that , under baseline conditions, the spontaneous firing was similar in hel pless rats and in non-helpless controls. However, neurons in the forme r group exhibited an enhanced sensitivity to the inhibitory action of the 5-HT reuptake blocker, citalopram (ED50 = 0.18 +/- 0.02 mg/kg IV i n helpless rats versus 0.27 +/- 0.03 mg/kg IV in controls, P < 0.05). Treatment with zimeldine during 3 consecutive days induced in both hel pless and control rats, a decrease in the inhibitory response of serot onergic neurons to the citalopram challenge, which resulted in a norma lization of the neuronal reactivity in the helpless group (ED50 = 0.31 +/- 0.03 mg/kg IV). Since this adaptive phenomenon parallels the beha vioural improvement induced by the repeated administration of zimeldin e and other antidepressants in helpless rats, it might be considered a s a crucial event in the mechanism of therapeutic action of these drug s.