Acute stress induces a differential increase of 5-HT-moduline (LSAL) tissue content in various rat brain areas

5-HT-moduline is an endogenous cerebral tetrapeptide (LSAL) which specifica lly interacts as an allosteric modulator with 5-HT1B receptors controlling serotonergic activity [O. Massot, J.C. Rousselle, M.P. Fillion, B. Grimaldi , I. Cloez-Tayarani, A. Fugelli, N. Prudhomme, L. Seguin, B. Rousseau, M. P lantefol, R. Hen, G. Fillion, 5-Hydroxytryptamine-moduline, a new endogenou s cerebral peptide, controls the serotonergic activity via its specific int eraction with 5-hydroxytryptamine1B/1D receptors, Mel. Pharmacol. 50 (1996) 752-762; J.C. Rousselle, O. Massot, M. Delepierre, E. Zifa, G. Fillion, Is olation and characterization of an endogenous peptide from rat brain intera cting specifically with the serotonergic1B receptor subtypes, J. Biol. Chem . 271 (1996) 726-735; J.C. Rousselle, M. Plantefol, M.P. Fillion, O. Massot , P.J. Pauwels, G. Fillion, Specific interaction of 5-HT-moduline with huma n 5-HT1b as well as 5-HT1d receptors expressed in transfected cultured cell s, Naunyn-Schmiedeberg's Arch. Pharmacol. 358 (1998) 279-286]. Cerebral tis sue contents of 5-HT-moduline were determined in various rat brain areas af ter an acute restraint stress, and after repetition of this stress, to exam ine whether or not mechanisms involving this peptide could be affected by s tress situations. The measurement of the peptide was carried out using spec ific polyclonal antibodies [B. Grimaldi, M.P. Fillion, A. Bonnin, J.C. Rous selle, O. Massot, G. Fillion, Immunocytochemical localization of neurons ex pressing 5-HT-moduline in the mouse brain, Neuropharmacology 36 (1997) 1079 -1087] in a dot-ELISA (enzyme-linked-immunosorbent assay) assay in cortex, hippocampus, hypothalamus, substantia nigra, striatum and in adrenal glands . Tissue contents of 5-HT-moduline progressively and transiently increased in most studied brain regions and reached a maximal value 20 min after the beginning of the restraint stress. The increase in 5-HT-moduline tissue con tents represented 323% of the value observed in unstressed control animals in the cortex. 207% in the hippocampus, 149% in the hypothalamus and 156% i n the substantia nigra. Thereafter, the peptide content of the latter tissu es diminished during the last 20 min of restraint and returned to control v alues within 1 h after the end of the stress period. The striatum did not s how any significant variation of 5-HT-moduline content during restraint str ess. In adrenal glands, the 5-HT-moduline content rapidly decreased (60% of controls) after the beginning of the restraint stress, the effect of this stress being progressively less pronounced, still representing 80% of contr ols after 40 min. Repetition of the restraint stress daily for 3 weeks tota lly abolished the effect of the stress on variations of 5-HT-moduline tissu e content in all the studied brain regions. These results show that an acut e restraint stress induces a rapid and significant increase in the amount o f 5-HT-moduline contained in various brain areas. This phenomenon is likely to be related to the stress-induced 5-HT1B receptor desensitization which was previously demonstrated. (C) 1999 Published by Elsevier Science B.V. Al l rights reserved.