Brain Research BUN&, Vol. 24, pp. 81 i-817. B Pergamon Press pk. 1990. Printed in the U.S.A. 0361-9230/90 $3.00 + .I0 Action of Neurotropin on Rat Hypothalamic Neurons in Tissue Slices zyxwvutsrqponmlk KIYOMI NAKAMURA, TAKETOSHI ONO,’ HISAO NISHIJO AND RYOI TAMURA Department zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA of zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Physiology, Faculty zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA of Medicine, Toyama Medical and Pharmaceutical Upliversi& ~5ya~ 935-51, Japan Received 3 April 1990 NAKA~~A, K., T. ONO, H. NISHIJO AND R. TAMURA. Action of ~eurotr~pin on rut ~ypo?hafa~ic ~e~ro~~in tissue slices. BRAIN RES BULL 24(6) 811-817, 1990.-To clarify some of the actions of Neurotropin (NSP), intra- and extracellular measurements were made of 140 paraventricular (PVN) and 48 ventromedial nucleus (VMH) neurons in rat hypothalamic tissue slices in vitro while perfusing NSP, an extract from the inflamed skin of rabbits inoculated with vaccinia virus, through the recording chamber. NSP mostly decreased activity in PVN neurons (inhibition, 46; excitation, 27; excitation-inhibition, 5; no response, 62). and mostly increased it in VMH neurons (excitation, 12; inhibition, 3; no response, 33). Inhibition of PVN neurons by NSP was due to hyperpolarization with no change in membrane conductance. Since ouabain antagonized the NSP-induced inhibition of PVN neurons, the effect was probably due to activation of the sodium pump. Activity of some NSP-responsive PVN neurons was increased by increase of extracellular osmolarity, and activity of some NSP-responsive VMH neurons was increased by glucose application. The results suggest central modulation of autonomic or neuroendocrinological function by distinct NSP influence on PVN and VMH neural activity. Neurotropin Autonomic nervous system Paraventricular nucleus Ventromedial nucleus Neural activity NEUROTROPIN (NSP), an extract isolated from the inflamed skin of rabbits inoculated with vaccinia virus, is isolated by deproteinization and several purification steps (26). NSP is re- ported to produce therapeutic effects by normalizing the auto- nomic nervous system and the immune system of an org~ism suffering from any of a variety of diseases, without discernibly affecting the organism’s normal functions (26,41). NSP has been indicated for more than 30 years for treatment of chronic diseases such as lumbago, shoulder-arm-neck syndrome, symptomatic neuralgia, pruritus as an accompanying manifestation of skin disease, and allergic rhinitis (26). The restorative action of NSP on bio~g~ato~ imbalance, such as vegetative dystonia caused by stress, has been demonstrated in animals subject to rhythmic alteration of temperature (SART-stressed animals) (24), or re- strained water immersion (RWIS animal) (14). NSP alleviated various abnormal conditions in SART-stressed and RWIS animals. The respective decrease and increase of acetylcholine (ACh) responses in duodena excised from SART-stressed (13) and RWIS animals (43), were both markedly inhibited by NSP (22,43). The actions of NSP, with slight exceptions, were considered to be primarily local at the cellular level (26). The exceptions were suggested by the SART and RWIS results, since stress may be mediated, at least in part, through the central nervous system (CNS). In SART-stressed animals, NSP signi~cantly i~ibited the decrease in the total ACh content in the hypothalamus and basal ganglia and inhibited the increase in the total ACh content in the duodenum. These facts suggested that the changes in the duode- num induced by SART stress were under the control of autonomic centers (12). Immunohistochemical investigation in the CNS made it clear that a neurotropic factor of NSP is incorporated into neurons or nerve fibers in the hy~~~arnus and limbic structures, and this incorporation is especially high in fiber terminals of the paraventricular nucieus (PVN) and in pyramidal cell bodies in the hippocampus (21). Among other things, the hypothalamus and limbic structures, including the PVN, integrate somatic, auto- nomic and endocrine reactions to maintain homeostasis, promote ~cu~ration of the body, conserve energy, and control digestion and excretion (1, 3, 4, 15, 38). Although these results suggest that the NSP regulatory effect on the autonomic nervous system, and its analgesic and sedative effects should be produced via neurons in the hypothalamus or limbic structures, there has been no investigation of this possibility at the single neuron level. In the present study, intra- and extracellular single neuron activity was recorded from the PVN and ventromedial (VMH) nuclei in rat hypothalamic tissue slices in vitro to explain some of the working functions of NSP perfused through the recording chamber. Preparation MPTHOD Eighty-four male albino Wistar rats weighing 80-120 g were used. Immediately after removal of the brain, it was placed, cortex ‘Requests for reprints should be addressed to Taketoshi Ono. 811