Serotoninergic mechanism underlying the dependence of some neurotropic effects of lithium hydroxybutyrate on circadian phase of administration

Abstract

Lithium hydroxybutyrate administered in the morning exhibits sedative effect, weakens memory consolidation, accelerates extinction of conditioned active avoidance reaction, and inhibits synthesis and catabolism of serotonin in the brain. When administrated in the evening, this drug apart from its sedative effect, improves learning and memory, prolongs memory retention, accelerates synthesis, and inhibits catabolism of serotonin.Key Words: lithium hydroxybutyrate; chronopsychopharmacology; serotoninergic system Lithium hydroxybutyrate (LHB) is a highly efficient normothymic preparation with pronounced rhythmmodulating activity [4,5]. This is a beneficial combination in light of the modern ehronobiological concept of affective disorders [1]. We have previously demonstrated that effect of LHB on circadian rhythms of spontaneous behavioral activity depends on the time (phase) of administration, initial biorhythms, and illumination regimen [4]. Some neurotropie properties of LHB determined by the presence of bioactive anionic component (hydroxybutyric acid) allows the use of this drug not only in affective disorders. However, phasic rhythm-modulating activity of LHB can affect its psychotropie effects. On the other hand, LHB induces adaptive rearrangements in the cerebral serotoninergie system [10]. Dysfunction of this system affects the formation of circadian rhythms [13]. It is known that circulatory psychoses are charaeterized by disordered structure of circadian rhythms [1] and impaired function of the serotoninergic system [9,111.These considerations prompted us to study semtoninergic mechanisms of phasic dependence of sedative and nootropie effects of LHB.