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H KO029Gc1J4 'I'ni: ( 'O)UNt •u. Ff )ir'I'I Ii:.%( .(•41 1dI:.LIL it-1L.ti..1.. 1.(•. ME7'K)RAPIDUf9 Septemter 10, 1980 T0: Drs. Binq, Ford, Hockett, Meier, Sonane.rs and Stone F%)M: W. U. Gardner SUBJELT: Ppplicatic+n 1223RIS. Kjell FuxE, The Karolinska Institute, Stockholm, Sweden. "Nicotine, CatecholamLines and Neuroendocrine Functions." Proaress. When nicoti^.c Nras administered it was usually given in doses of 1-2 mg g~ s at 30-minute intervals. The pituitary hormones were determined in blood by RIA. In thyroidectanized rats, nicotine prevented the increase of TSH and PRO in the blood due to reduction of catecholami,ne levels in the medial zone of the median etninence. Nicotine facilitated the increase of M secretion in rats given pentobarbital. The central mec]zanisms probably act through dopwnine depletion in special areas of the CN5. The t-arnover rates in special areas of the Q4S were also followed after the intraveitsicular injection of small amrnmts of nicotine. Nicotine increased cortisone secretio.i; mee.amylam.inE in adeguate doses inhibited this response. Further studies with mecamylamine and nicotine indicated that two different nicotine responses ma}• exist in the CNS. Studies with a dopamine b1o-Jkung agent, pvrozide, sha•red the inhibition of the PRO blocking effect of nicotine. 6-hydroxy-dopamine injected into the te3mentum reduced the mmnber of A and NA terminais in the h),pothalannus and prevented PRO inhibition. Nbst of these observations were surmarized in tabular form. Projection. Because of leads frcm research undertaken to date, work will continue on the tuber-infunriibular systems and cigarette smoke exposure will be use.l instead of nicotine injections. In addition, nicotine will be given by osmopumps. Further work will be donc on the aFpar?nt tiao types of nicotine-like cholinerqic receptors. 7n addition to me:.an•laminc, hexamethonium and d-tubocurarine will be injected in the ventricles. Selective lesioning of the nucleus coeruleus will be done chanicall}• by the use of DSP-4 (n-chloroethyl-n-eth}•1-3-bromberizolamine) and in the arcuate nuclear area b}• ibotenic acid. The chronic administration of nicotine itself or in ciaarette snoke will be the major innoA•ation. Dr. Samiers made a site visit in June. Budget. A modified budqet has been ieceived - $67,356. 'a'he increase ($13, 356) resulted from salaxy increases and fran the purchase of the osnnnimm';. 1„ t-,Ln waj-.L sent two Walton Horizontal Smokirg P7achines u-ith holders for rats on a loan basis. Gne Walton will be used for srmke exposures. Qcammt. Ne reprint ar.d three nanuscriFts were sulTLittFd k^ tl1 the rei.,ert. Ra~tasm as hiah For both relevance and merit. W. U. G3rdncr 1ti1C- : ek