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T111i C(1l'1CIL FOR TOBACCO REFIiARI'll-U.S.A., INC. ?uly 24, 1979 MErtnRANDUM f TO: Prs. Bing, Ford, Hockett, Meier, Somm~•rs and Stone FROM: W. U. Gardner N QV2JG168 SUBJECI: Applicat-inn 1223R1. fijel] Fuxe, The Karolinsl.a Institute, and Hormone Lab. harelinsl,a Hospital, Stockholm, Sweden. "Nicotine, Catechoiamines and 1leuroendocrine 1'unctinns." NA - noradrenalin Lact. lj. - lactogenic hormone DA - dnpamine GH - growth hormone TSH - thyroid stimulating hormone LH - leutinizin¢ hormone Progress. Two manuscripts were submitted: (1) nicotine depletes adrenalin stores in the hypothalamus and increases adrenalin turnover in the hypothalamus of normal male rats. Adrenalin may be involved as mediator for the neuroendocrine actions of nicotine. (2) relates to effects of nicotine to central catecholamine neurones and gonadotropin secretion and TSH secretion in castrated male rats. NA and PA turnovers were modified in some h+pothalamic nuclei. TSH and Lact. H were reduced but not LH and FSH. in general, the castrated males showed effects cimi]a: to ovariect9mized rats. Nicotine reduced growth hn>.mone secretinn in oti'ariectomized rats. This was counteracted by pretreatement with low dnses of inecamylamine. A cholinergic nirotine-l:ke receiptor may be involved in GH secrction. Proiection. The effects of repeated ltigh doses of nicotine on the blood level: of LH, FSH, TSH and GH will be determined in the sume animal and correlated with changes in catechilamine stores and turnover, particularly on the h~?othalamus. A tyrosine hydrox+lase inhibitor (Ha4/68) will be used to abet studies of CA turnovcr. Dopamine turnovers can also be abetted by en:.yme inhibitors. Ptccamylamine, whicn does not nass the blood-brain harrier efficiently probahly acts at the level of the median eminence. This may la.:alize some cholinergic nicotine•Me receiptors. Pharmacological hlocking agents will be =tudied further as mediators for the blocl,ing of lactogenic hormone, LH, TSH, FSH and GH. Lesions of the CA pat'atiays will be made to determine nicotine-induced inhibition of the above hormones. Studies will be done on the effects of nicotine in rate iniected with PSP-4 (N-(2-clilproeth••]1-N-eth%•1-2-hrc+mo-hen:%, lamine) t,liicL produce5 conplete depeneration of all P:A s+•stemG originattng from the 1ccu- ceriileus. Studies are a~so planned on the effects of the intraventricul,-r iniectio:t of nicetine on hormone production. A speci;.1 study of the effects of tticotine on ACTH and corticosteronc is also planned. lhe• effects of chronit nicotine treatment of rats via the iuFular vein using unanrs*heticed rats will he cr:,dicd. RudFet. Ile is reqneatinF i;2,000 more tli:tn proiected. Salaries are `iifh in Si+eden. They get asmal t contri hitt ion from t he Swedi 5h Tohacco Cotmci 1. -+'. 11. i,lrdner klh ;, I,