The Biochemical and Functional Nature of the Nicotine Receptor in Rat Brain
An investigation has been undertaken of the biochemical nature and neuroanatomical localization of the sites involved in nicotine’s action on the brain. The present report describes studies aimed at 1) the characterization and purification of the nicotine receptor in rat brain; 2) elucidating the psychopharmacologic nature of the receptor using various nicotine analogues and other psychotropic agents; and 3) determining the particular brain regions directly involved in the behavioral effects (e.g., prostration and seizures) of nicotine. The nicotine receptor, which has been purified by affinity chromatography and consists of a major protein with a molecular weight of 58 kdalton and minor components ranging from 47 to 83 kdaltons, does not appear to resemble the nicotinic cholinergic receptor purified from the electric fish. The functional significance of the nicotine receptor has been confirmed by correlating the psychotropic potency of various nicotine analogues with their affinity for the receptor. Evidence is presented for the existence of multiple forms of both the nicotine and nicotinic cholinergic receptors by comparing the binding and psychotropic characteristics of some carbamate esters, nicotine analogues, and various unrelated drugs acting as antagonists to nicotine. In order to determine its neuroanatomical site of psychotropic action, nicotine was injected into cannulae chronically implanted into various brain regions of conscious, freely moving rats. It appears that the primary locus is the vestibular system, particularly that component linked to the cerebellar nodule. Lesioning the cerebellar nodule or inhibiting it with a local anesthetic abolishes the nicotine-induced prostration and increases the number of nicotine and muscarinic cholinergic receptors in hypothalamus and caudate nucleus. It is proposed that the vestibular system, which plays a major role in the processing of sensory-motor information may be involved in the reinforcing and other affective effects of nicotine in man.
KeywordsNicotine Receptor Fourth Ventricle Vestibular Nucleus Kainic Acid Vestibular System
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