Early Life Blockade of 5-Hydroxytryptamine 1A Receptors Normalizes Sleep and Depression-Like Behavior in Adult Knock-Out Mice Lacking the Serotonin Transporter

摘要: In serotonin transporter knock-out (5-HTT-/-) mice, extracellular (5-HT) levels are markedly elevated in the brain, and rapid eye movement sleep (REMS) is enhanced compared with wild-type mice. We hypothesized that such impairment at adulthood results from excessive serotonergic tone during early life. Thus, we assessed whether neonatal treatment drugs capable of limiting impact 5-HT on brain could normalize patterns 5-HTT-/- mutants. found treatments initiated postnatal day 5 continued for 2 weeks synthesis inhibitor para-chlorophenylalanine, or 4 5-HT(1A) receptor (5-HT(1A)R) antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide (WAY 100635), induced total partial recovery REMS, respectively, Early life WAY 100635 also reversed depression-like behavior otherwise observed these Possible adaptive changes 5-HT(1A)R after were investigated by measuring binding sites mRNA various REMS- and/or depression-related areas, as well 5-HT(1A)R-mediated hypothermia inhibition neuronal firing dorsal raphe nucleus. None characteristics modified parallel REMS recovery, suggesting 5-HT(1A)Rs involved phenotype rescue mutants located other areas 5-HT(1A)R-unrelated circuits where they be transiently expressed development. The reversal alterations blockade might open new perspectives regarding preventive care mood disorders resulting impairments