Alcohol
Volume 20, Issue 1 , Pages 19-29 , January 2000

Effects of phentermine and fenfluramine on alcohol consumption and alcohol withdrawal seizures in rats

  • A.K. Halladay

      Affiliations

    • Department of Psychology, Rutgers University, New Brunswick, NJ 08904, USA
  • ,
  • H. Fisher

      Affiliations

    • Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ 08904, USA
  • ,
  • G.C. Wagner

      Affiliations

    • Department of Psychology, Rutgers University, New Brunswick, NJ 08904, USA
    • Corresponding Author InformationCorresponding author. Tel.: 732-445-4660; Fax: 732-445-2263

Received 2 February 1999 ,Revised 29 May 1999 ,Accepted 2 June 1999.

References 

  1. Balcioglu A, Wurtman RJ. Dexfenfluramine enhances striatal dopamine release in conscious rats via a serotonergic mechanism. J Pharm Exp Ther. 1998;284:991;a
  2. Balcioglu, A., & Wurtman R. J. (1998b). Effects of fenfluramine and phentermine (fen-phen) on dopamine and serotonin release in the rat striatum: in vivo microdialysis study in conscious animals. Br Res, 67–72.
  3. Bonanno G, Fassio A, Severi P. Fenfluramine releases serotonin from human brain nerve endings by a dual mechanism. J Neurochem. 1994;63:1163
  4. Bono G, Balducci C, Richelmi P, Koob GF, Pulvirenti L. Dopamine partial receptor agonists reduce ethanol intake in the rat. Eur J Pharmacol. 1996;296:233–239
  5. Brauer L, Johanson C, Schuster C, Rothman R, de Wit H. Evaluation of phentermine and fenfluramine, alone and in combination, in normal, healthy volunteers. Neuropsychopharmacol. 1996;14:233–241
  6. Di Chiara G, Acqua E, Tanda G. Ethanol as a neurochemical surrogate of convential reinforcers (the dopamine-opioid link). Alcohol. 1996;13:13–17
  7. Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA. 1988;85:5274–5278
  8. Feinman L, Leiber CS. Nutrition (medical complications of alcoholism). In:  Leiber CS editors. Medical and Nutritional Complications of Alcoholism. New York, NY: Plenum Press; 1992;p. 515–517
  9. Fisher H, Yu Y-L, Sekowski A, Federico E, Ulman E, Wagner GC. Diet Composition, alcohol utilization and dependence. Alcohol. 1996;13:195–200
  10. Fuller RW, Perry KW, Clemens JA. Elevation of 3,4-dihydroxyphenylacetic acid concentrations in rat brain and stimulation of prolactin secretion by fenfluramine (evidence for antagonism at dopamine receptor sites). J Pharm Pharmac. 1976;28:643–644
  11. Gil-Martin E, Colado I, Fernandez-Lopez A, Fernandez-Briera A, Calvo P. Effects of an acute dose of ethanol on dopaminergic and serotonergic systems from rat cerebral cortex and striatum. Comp Biochem Physiol. 1996;113C:399–402
  12. George SR, Fan T, Jungs SU, O'Dowd BF, Naranjo CA. Low endogenous dopamine function in brain predisposes to high alcohol preference and consumption (reversal by increasing synaptic dopamine). J Pharmacol Exp Ther. 1995;273:373–379
  13. Glowa J, Rice K, Mateka D, Rothman R. Phentermine/fenfluramine decreases cocaine self-administration in rhesus monkeys. Neuro Rep. 1997;8:1347–1351
  14. Gulley J, McNamara C, Barbera T, Ritz M, George F. Selective serotonin reuptake inhibitors (effects of chronic treatment on ethanol-reinforced behavior in mice). Alcohol. 1995;12:77–181
  15. Halladay AK, Fisher H, Wagner GC. Interaction of phentermine plus fenfluramine (neurochemical and neurotoxic effects). Neurotoxicol. 1988;19:177–184
  16. Higgins G, Tomkins D, Fletcher P, Sellers E. Effect of drugs influencing 5-HT function on ethanol drinking and feeding behavior in rats (studies using a drinkometer system). Neurosci Biobehav Rev. 1992;16:535–552
  17. Hitzig P. Combined serotonin and dopamine indirect agonists correct alcohol craving and alcohol-associated neuroses. J Subst Abuse Treat. 1994;11:489–490
  18. Hitzig P. Combined dopamine and serotonin agonists (A synergistic approach to alcoholism and other addictive behaviors). Md Med J. 1993;42:153–156
  19. Howell L, Czoty P, Byrd L. Pharmacological interactions between serotonin and dopamine on behavior in the squirrel monkey. Psychopharmacol. 1997;131:40–48
  20. Koetzner L, Riley AL, Glowa JR. Discriminative stimulus effects of dopaminergic agents in rhesus monkeys. Pharmacol Biochem Behav. 1996;54:517–523
  21. Koob G. Drug Addiction (the yin and yang of hedonic homeostasis). Neuron. 1996;16:893–896
  22. Koob G, Bloom FE. Cellular and molecular mechanisms of drug dependence. Science. 1988;242:715–723
  23. Imperato A, Di Chiara G. Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther. 1986;239:219–228
  24. Leville GA, Chakrabarty K. Absorption and utilization of glucose by meal-fed and nibbling rats. J Nutr. 1968;96:69–75
  25. Linnoila M. Alcohol withdrawal syndrome and sympathetic nervous system function. Alcohol Health Res World. 1989;13:355–357
  26. Loscher W, Lehmann H, Teschendorf H-J, Traut M, Gross G. Inhibition of monoamine oxidase type A, but not type B, is an effective means of inducing anticonvulsant activity in the kindling model of epilepsy. J Pharmacol Exp Ther. 1999;288:984–992
  27. Lu M-R, Wagner GC, Fisher H. Ethanol consumption following acute treatment with methysergide, fluoxetine, fenfluramine and their combination. Alcohol Clin Exp Res. 1994;18:60–63
  28. Lu M-R, Wagner GC, Fisher H. Ethanol consumption following acute fenfluramine, fluoxetine, and dietary tryptophan. Pharmacol Biochem Behav. 1993;44:931–937
  29. Lucas JJ, Yamamoto A, Scearce-Levie K, Saudou F, Hen R. Absence of fenfluramine-induced anorexia and reduced c-fox induction in the hypothalamus and central amygdaloid complex of serotonin 1B receptor knock-out mice. J Neurosci. 1998;18:5537–5544
  30. Lyness W, Smith F. Influence of dopaminergic and serotonergic neurons on intravenous ethanol self-administration in the rat. Pharmacol Biochem Behav. 1992;42:187–192
  31. Maher TJ, Ulus IH, Wurtman RJ. Phentermine and other monoamine-oxidase inhibitors may increase plasma serotonin when given with fenfluramines. Lancet. 1999;353:38–1999
  32. Mirovsky Y, Wagner GC, Sekowski A, Goldberg M, Fisher H. Novel synergistic treatment of ethanol withdrawal seizures in rats with dopamine and serotonin agonists. Alcohol: Clin Exp Res. 1995;19:160–163a
  33. Mirovsky Y, Wagner GC, Sekowski A, Goldberg M, Fisher H. Simultaneous changes in striatal dopamine, serotonin, and metabolites after withdrawal seizures in rats from dependence on alcohol. Alcohol. 1995;12:251–256b
  34. Munzar P, Baumann MH, Shoiab M, Goldberg SR. Effects of dopamine and serotonin releasing agents on methamphetamine discrimination and self-administration in rats. Psychopharmacol. 1999;141:287–295
  35. Olds M, Yuwiler A. Effects of acute and chronic fenfluramine on self-stimulation and its facilitation by amphetamine. Eur J Pharmacol. 1992;216:363–372
  36. Papasava M, Singer G, Papasava CL. Intravenous self-administration of phentermine in food-deprived rats (effects of abrupt refeeding and saline substitution). Pharmacol Biochem Behav. 1986;25:623–627
  37. Pfeffer AO, Samson HH. Haloperidol and apomorphine effects on ethanol reinforcement in free feeding rats. Pharmacol Biochem Behav. 1988;29:343–350
  38. Rea WP, Rothman RB, Shippenberg TS. Evaluation of the contitioned reinforcing effects of phentermine and fenfluramine in the rat (concordance with clinical studies). Synapse. 1998;30:107–111
  39. Rossetti Z, Melis F, Carboni S, Diana M, Gessa GL. Alcohol withdrawal in rats is associated with a marked fall in extraneuronal dopamine. Alcohol: Clin Exp Res. 1992;16:529–532
  40. Roth JD, Rowland NE. Efficacy of administration of dexfenfluramine and phentermine, alone and in combination, on ingestive behavior and body weight in rats. Psychopharmacol. 1998;137:99–106
  41. Rothman R, Ayestas M, Baumann MH. Phentermine pretreatment antagonizes the cocaine-induced rise in mesolimbic dopamine. Neuro Rep. 1996;8:7–9
  42. Rothman R. Smoking cessation in a patient being treated with fenfluramine plus phentermine for simple obesity. J Clin Psychiatry. 1996;57:92–93
  43. Rouillard C, Bovetto S, Gervais J, Richard D. Fenfluramine-induced activation of the immediate-early gene c-fos in the striatum (possible interaction between serotonin and dopamine). Br Res Mol Br Res. 1996;37:105–115
  44. Samochoweic J, Kleinrok Z, Horodnicki J. The role of dopamine neurotransmission in ethanol dependence development and withdrawal in rats. Pharmazie. 1995;50:815–817
  45. Schecter MD, McBurnery D. Phentermine + fenfluramine produce cocaine-like discriminative cues. Life Sci. 1996;59:303–308
  46. Sellers E, Higgins G, Sobell M. 5-HT and alcohol abuse. Trend Pharmacol Sci. 1992;13:69–75
  47. Shoaib M, Baumann MH, Rothman RB, Goldberg SR, Schindler CW. Behavioral and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats. Psychopharmacol. 1997;131:296–306
  48. Weintraub, M., Sundaresan, P., Schuster, B., Moscucci, M., Stein, E. (1992). Long-term weight control study III. Clin Pharmacol Ther 51, 602–646.
  49. Weiss F, Lorang MT, Bloom FE, Koob GF. Oral alcohol self-administration stimulates dopamine in the rat nucleus accumbens (genetic and motivational determinants). J Pharmacol Exp Ther. 1993;267:250–267
  50. Weiss F, Parsons L, Schulteis G, Hyytia P, Lorang M, Bloom F, et al. Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J Neurosci. 1996;16:3474–3485
  51. Woods J, Druse M. Effects of chronic ethanol consumption and aging on dopamine, serotonin and metabolites. J Neurochem. 1996;66:2168–2178
  52. Yoshimoto K, McBride WJ, Lumeng L, Li T-K. Alcohol stimulates the release of dopamine and serotonin in the nucleus accumbens. Alcohol. 1991;9:17–22
  53. Yu Y-L, Fisher H, Sekowski A, Wagner GC. Amphetamine and fenfluramine suppress ethanol intake in ethanol-dependent rats. Alcohol. 1996;14:45–48
  54. Zacek R, Battaglia G, Culp S, Appel NM, Contrera JF, DeSouza EB. Effects of repeated fenfluramine administration on indices of monoamine function in rat brain (pharmacokinetic, dose response, regional specificity and time course data). J Pharm Exp Ther. 1990;253:104–112
  55. Zhou F, Zhang J, Lumeng L, Li T-K. Mesolimbic dopamine system in alcohol-preferring rats. Alcohol. 1995;12:403–412
  56. Zhou F, Lu C, Murphy J, Lumeng L, Li T-K. Serotonergic neurons in alcohol preferring rats. Alcohol. 1994;11:397–403

PII: S0741-8329(99)00047-6

Alcohol
Volume 20, Issue 1 , Pages 19-29 , January 2000