Brain Research, 205 (1981) 445-451 445 © Elsevier/North-Holland Biomedical Press Increase in histamine concentrations in discrete hypothalamic nuclei of spontaneously hypertensive rats FERNANDO M. A. CORREA* and JUAN M. SAAVEDRA** Section on Pharmacology, Laboratory of Clinical Science, National Institute of Mental Health, Bethes- da, 20205 (U.S.A.) (Accepted September 4th, 1980) Key words: histamine - - brain - - hypothalamus - - genetic hypertension Histamine meets many of the criteria which must be satisfied in order to consider a compound as a neurotransmitter in the central nervous system (CNS). It is localized in synaptosomes after subcellular fractionation of brain tissue is. Discrete histaminer- gic pathways have been described in the brain 10. Endogenous histamine can be re- leased from brain slices by depolarizing the nerve cells with potassium as. Iontophore- sis of histamine modifies the action potentials of cerebral neurons 25. When injected in- traventricularly 27 or directly into discrete brain areas 12, histamine has potent effects on neuronal activity. In addition, histamine receptors 7 and a histamine-sensitive adenyla- te cyclase la have recently been characterized in the brain. Pharmacological evidence indicates that histamine has centrally mediated effects on blood pressure2,14,as, 37. These observations suggest that endogenous brain hista- mine could play a role in the regulation of blood pressure or in the pathogenesis of hy- pertension. Selective changes in catecholamine metabolism, discretely localized to a few nu- clei and areas of the brain, had been found in several models of hypertension 2s-a0. A similar situation could be envisioned for other putative neurotransmitters such as his- tamine. We have attempted the quantitation of endogenous histamine levels in those discrete brain areas which are part of the principal central pathways regulating cardio- vascular functions in mammals. The study was conducted at two stages of the devel- opment of the genetic hypertension using young (4 weeks old) and adult (12 weeks old) spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto rats, WKY)ZL These ages were selected for their difference in manifested high blood pressure and because there are age-specific changes in catecholamine metabolism in si- milar brain structures29, so. * On leave from Department of Pharmacology, School of Medicine, Ribeirao Preto, Sao Paulo, Brazil. ** To whom all correspondence should be addressed.