Preference for alcohol evoked by tetrahydropapaveroline (THP) chronically infused in the cerebral ventricle of the rat

作者: Christine L. Melchior , R.D. Myers

DOI: 10.1016/0091-3057(77)90006-5

关键词: Blood alcoholAlcoholInternal medicineSaccharinTetrahydropapaverolineFluid intakeMedicineAnesthesiaMetaboliteEndocrinologyCerebral ventricleAlkaloidToxicologyClinical biochemistryBiochemistryBiological psychiatryBehavioral neurosciencePharmacology

摘要: Abstract The voluntary preference for ethyl alcohol in Sprague-Dawlet rats was determined over 12 days with water as the alternative fluid. solutions offered to animals were increased systematically concentrations from 3 30%, according a three-bottle, two-choice technique. Tetrahydropapaveroline (THP), tetrahydroisoquinoline derivative, infused repeatedly into lateral cerebral ventricle of each rat through guide tube implanted chronically. metabolite dissolved CSF vehicle, and volume 1.0 μl every 15 min or 4.0 30 around clock, entire 12-day period alcohol-water self-selection. Within 6 start infusion, extraordinary amounts consumed which ranged high 8 17 g per kg day. Both racemic mixture THP S-(-)-THP isomer exerted this alcohol-inducing effect, when they chronically range doses 100 picograms/μl mu;g/μl. Control intraventricular infusions same regimen had no effect on preference. excessive intake during persisted long after cessation infusion regimen, i.e., retests carried out at one, six nine months' intervals. Further, THP-treated simultaneous choice palatable solution saccharin together alcohol, continued drink large volumes alcohol. 24 hr patterns fluid intake, registered continuously by drinkometer, revealed that drinking typically massed within two four bouts night-time interval. During period, blood level reached 0.2%. Withdrawal-like symptoms including wet-dog shakes, elevated tail, whisker twitching occasional convulsive episodes, also observed THP-infused rats. These findings provide support hypothesis an alkaloid metabolite, may be formed both brain periphery, is involved mechanism underlying pathological sustained characteristic disease state alcoholism.

参考文章(44)
Kenneth M. Baker, Sergio Algeri, Alberto Frigerio, Silvio Garattini, Anthony J. Turner, Tetrahydropapaveroline: formation in vivo and in vitro in rat brain. Life Sciences. ,vol. 14, pp. 2247- 2257 ,(1974) , 10.1016/0024-3205(74)90106-4
G. D. Frye, J. B. Lucot, J. D. Leander, F. W. Ellis, D. E. McMillan, Characteristics of Ethanol Drinking Patterns under Schedule-Induced Polydipsia Psychopharmacology. ,vol. 49, pp. 49- 55 ,(1976) , 10.1007/BF00427470
P J O'Neill, R G Rahwan, Absence of formation of brain salsolinol in ethanol-dependent mice. Journal of Pharmacology and Experimental Therapeutics. ,vol. 200, pp. 306- 313 ,(1977)
Wei E, Loh Hh, Way El, BRAIN SITES OF PRECIPITATED ABSTINENCE IN MORPHINE-DEPENDENT RATS Journal of Pharmacology and Experimental Therapeutics. ,vol. 185, pp. 108- 115 ,(1973)
P.V. Halushka, P.C. Hoffmann, Does tetrahydropapaveroline contribute to the cardiovascular actions of dopamine Biochemical Pharmacology. ,vol. 17, pp. 1873- 1880 ,(1968) , 10.1016/0006-2952(68)90103-2
G.E. Martin, R.D. Myers, Ethanol ingestion in the rat induced by rewarding brain stimulation Physiology & Behavior. ,vol. 8, pp. 1151- 1160 ,(1972) , 10.1016/0031-9384(72)90212-0
R. Myers, C. Melchior, Alcohol drinking: abnormal intake caused by tetrahydropapaveroline in brain Science. ,vol. 196, pp. 554- 556 ,(1977) , 10.1126/SCIENCE.557839
Kenneth Blum, Joseph D. Eubanks, Jack E. Wallace, Harvey Schwertner, William W. Morgan, POSSIBLE ROLE OF TETRAHYDROISOQUINOLINE ALKALOIDS IN POSTALCOHOL INTOXICATION STATES Annals of the New York Academy of Sciences. ,vol. 273, pp. 234- 246 ,(1976) , 10.1111/J.1749-6632.1976.TB52887.X
P. P. Laidlaw, The action of tetrahydropapaveroline hydrochloride The Journal of Physiology. ,vol. 40, pp. 480- 491 ,(1910) , 10.1113/JPHYSIOL.1910.SP001384