5-hydroxytryptamine-moduline: A novel endogenous peptide involved in the control of anxiety

The serotonergic system is considered as a neuromodulatory system interacti ng with other neurotransmissions in the brain and participating in the elab oration of an adapted response of the central nervous system to external st imuli. Indeed, serotonin is involved in a large number of physiological eve nts, such as temperature regulation, sleep, learning and memory, behaviour, sexual function, hormonal secretions and immune activity, and in parallel, it is also implicated in pathological disorders particularly in stress, an xiety, aggressivity and depression.(15) At least 14 different types of sero tonin receptors mediate serotonergic activity and among them, serotonin-1B receptors play an important role in the control of the serotonergic functio n.(8,10) Serotonin-1B receptors are autoreceptors localized on serotonergic neuron terminals (varicosities) where they inhibit the evoked release of s erotonin and its biosynthesis;(5,9) they are also heteroreceptors located o n non-serotonergic terminals, where they inhibit the release of the corresp onding neurotransmitters (acetylcholine, GABA, noradrenaline, etc.). 5-Hydr oxytryptamine-moduline, an endogenous tetrapeptide (Leu-Ser-Ala-Leu) recent ly isolated and characterized from rat and bovine brain extracts, was shown to specifically interact with serotonin-1B receptors as an allosteric modu lator having antagonistic properties in vitro and in vivo.(4,11,12) Immunoc ytochemical studies using specific polyclonal anti-peptide antibodies have shown that this peptide is distributed heterogeneously in mouse brain and l ocated in areas which also contain serotonin-1B receptors.(7) Moreover, the content of these cerebral tissues in 5-hydroxytryptamine-moduline is affec ted by stress.(2) In the present work, polyclonal anti-5-hydroxytryptamine- moduline antibodies were administered to mice via intracerebroventricular i njections to study the in vivo effects of a lowering (or suppression) of th is neuropeptide in the central nervous system. The inactivation of the pept ide by the specific antibodies significantly modified the behaviour of the animals in two behavioural tests, the open-field and elevated plus-maze, kn own to be animal models related to anxiety behaviour.(6) Treated mice displ ayed behaviour consistent with an anxiolytic effect of the antibody, sugges ting a potential role of 5-hydroxytryptamine-moduline in the control of anx iety. (C) 1999 IBRO. Published by Elsevier Science Ltd.