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 antidepressants have shown that both deprivation of rapid eye movement (REM) sleep and chronic treatment with antidepressants render serotoninergic (5-HT) neurons less sensitive to the inhibitory effect of 5-HT reuptake blockers in the rat. It was of interest to test whether the same mechanisms could be evidenced in a possible experimental model of depression. The latter consisted of rats which had been treated neonatally with clomipramine and exhibited at adult age behavioural and sleep alterations which resemble the human disorder. Recording the electrophysiological activity of 5-HT neurons in the nucleus raphe dorsalis (NRD) revealed that both chronic treatment with zimelidine and REM sleep deprivation induced a hyporeactivity of these neurons to the inhibitory effect of citalopram in "normal" rats. However, in rats which had been treated neonatally with clomipramine, 5-HT neurons were hyporeactive to the effect of this 5-HT reuptake blocker already under baseline conditions, and no further modification could be induced by chronic zimelidine administration or REM sleep deprivation. It can be hypothesized that adaptive phenomena at the serotoninergic NRD level are not a relevant element to explain the mechanism of action of anti-depressants in the present model of depression, while they have been considered as a crucial event in "normal" rats.
Maudhuit
C
C
INSERM U288, CHU Pitié-Salpêtrière, Paris, France.
Hamon
M
M
Adrien
J
J
D000818:Animals; D015283:Citalopram / Q000494:pharmacology; D002997:Clomipramine / Q000494:pharmacology; D003863:Depression / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012892:Sleep Deprivation / Q000502:physiology*; D015031:Zimeldine / Q000494:pharmacology*
D015283:Citalopram; D002997:Clomipramine; D017367:Selective Serotonin Reuptake Inhibitors; D015031:Zimeldine