EFFECTS OF CHRONIC TREATMENT WITH ZIMELIDINE AND REM-SLEEP DEPRIVATION ON THE REGULATION OF RAPHE NEURONAL-ACTIVITY IN A RAT MODEL OF DEPRESSION

Electrophysiological investigations on the mechanism of action of anti depressants have shown that both deprivation of rapid eye movement (RE M) sleep and chronic treatment with antidepressants render serotoniner gic (5-HT) neurons less sensitive to the inhibitory effect of 5-HT reu ptake blockers in the rat. It was of interest to test whether the same mechanisms could be evidenced in a possible experimental model of dep ression. The latter consisted of rats which had been treated neonatall y with clomipramine and exhibited at adult age behavioural and sleep a lterations which resemble the human disorder. Recording the electrophy siological activity of 5-HT neurons in the nucleus raphe dorsalis (NRD ) revealed that both chronic treatment with zimelidine and REM sleep d eprivation induced a hyporeactivity of these neurons to the inhibitory effect of citalopram in ''normal'' rats. However, in rats which had b een treated neonatally with clomipramine, 5-HT neurons were hyporeacti ve to the effect of this 5-HT reuptake blocker already under baseline conditions, and no further modification could be induced by chronic zi melidine administration or REM sleep deprivation. It can be hypothesiz ed that adaptive phenomena at the serotoninergic NRD level are not a r elevant element to explain the mechanism of action of antidepressants in the present model of depression, while they have been considered as a crucial event in ''normal'' rats.