, Volume 75, Issue 4, pp 358–362 | Cite as

Alteration of the disruptive effect of fenfluramine on food consumption in the rat by repeated post-session administration of d-amphetamine

  • Ronald N. Hunsinger
  • T. Bradford Barnes
  • John C. Kapeghian
  • Marvin C. Wilson
Original Investigations


The purpose of this study was to determine whether repeated treatment (15 days) with d-amphetamine (AMP) or fenfluramine (FEN), administered after a daily 3 h feeding session (e. g. post-session), would result in tolerance or crosstolerance to the decrement in food consumption induced by treatment with either drug before feeding (e. g. pre-session). Groups of male rats were treated IP with 0.5 ml saline, 1.0, 2.0, or 4.0 mg/kg AMP, or 2.5, 5.0, or 10.0 mg/kg FEN prior to a 3 h feeding session. For the next 15 sessions, the respective groups were treated post-session with saline (0.5 ml), AMP (4.0 mg/kg), or FEN (10 mg/kg). Following the 15 day postsession phase, each group again received this pre-session treatment. The initial pre-session treatment with all dosages of these two drugs produced a significant decrease in food consumption. Tolerance to the food intake suppressant effect of FEN, but not AMP, resulted from repeated post-session treatment with the same agent. Repeated post-session treatment with AMP resulted in a significant decrement in the suppressant activity of FEN on food intake, whereas the corresponding post-session treatments with FEN did not alter the pre-session effects of AMP, except for an enhancement seen with higher AMP doses.

Key words

d-Amphetamine Cross-tolerance Fenfluramine Food consumption Rats Tolerance 


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  1. Blundell JE, Latham CJ (1978) Possible influences of serotonin and dopamine on food intake. In: Garattini S, Samanin R (eds) Central mechanisms of anorectic drugs Raven Press, New York, pp 83–110Google Scholar
  2. Blundell JE, Latham CJ (1980) Characterization of adjustments to the structure of feeding behavior following pharmacological treatment: effects of amphetamine and fenfluramine and the antagonism produced by pimozide and methergoline. Pharmacol Biochem Behav 12:717–722Google Scholar
  3. Blundell JE, Leshem MB (1975) The effect of 5-hydroxytryptophan on food intake and on the anorexic action of amphetamine and fenfluramine. J Pharm Pharmacol 27:31–37Google Scholar
  4. Browne RG, Segal DS (1977) Metabolic and experimental factors in the behavioral response to repeated amphetamine. Pharmacol Biochem Behav 6:542–552Google Scholar
  5. Carlton PL, Wolgin DL (1971) Contingent tolerance to the anorexigenic effects of amphetamine. Physiol Behav 7:221–223Google Scholar
  6. Cooper SJ, Francis RL (1979) Feeding parameters with two food textures after chlordiazepoxide administration, alone or in combination with d-amphetamine or fenfluramine. Psychopharmacology 62:253–259Google Scholar
  7. Funderbunk WH, Hazelwood JC, Ruckhart RT, Ward JW (1971) Is 5-hydroxytryptamine involved in the mechanisms of action of fenfluramine? J Pharm Pharmacol 23:468–469Google Scholar
  8. Garattini S, Borroni E, Mennini T, Samanin R (1978) Differences and similarities among anorectic agents. In: Garattini S, Samanin R (eds) Central mechanisms of anorectic drugs. Raven Press, New York, p 128Google Scholar
  9. Ghosh MN, Parvathy S (1976) Tolerance pattern of the anorexigenic action of amphetamine, fenfluramine, phenmetrazine and diethylpropion in rats. Br. J Pharmacol 57:479–485Google Scholar
  10. Jaffe JH (1980) Drug addiction and drug abuse. In: Gilman AC, Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics, 6th ed. MacMillan Pub Co Inc., New York, pp 537–538Google Scholar
  11. Jesperson S, Scheel-Kruger J (1973) Evidence for a difference in the mechanism of action between fenfluramine and amphetamine. J Pharm Pharmacol 25:49–54Google Scholar
  12. Jonsson J (1977) On the aromatic hydroxylation of amphetamine in rat liver microsomes and perfused liver preparations: effects of long term administration. Acta Pharmacol Toxicol 4:517–528Google Scholar
  13. Jori A, Caccia S, Dolfine E (1978) Tolerance to anorectic drugs. In: Garattini S, Samanin R (eds) Central mechanisms of anorectic drugs. Raven Press, New York, pp 179–190Google Scholar
  14. Kandel D, Doyle D, Fischman MW (1975) Tolerance and cross-tolerance to the effects of amphetamine, methamphetamine and fenfluramine on milk consumption in the rat. Pharmacol Biochem Behav 3:705–707Google Scholar
  15. LeDouarec JC, Neveu C (1970) Pharmacology and biochemistry of fenfluramine. In: Costa E, Garrattini S (eds) Amphetamine and related compounds. Raven Press, New York, pp 75–106Google Scholar
  16. Lewander T (1978) Experimental studies on anorexigenic drugs: tolerance, cross-tolerance and dependence. In: Garattini S, Samanin R (eds) Central mechanisms of anorectic drugs. Raven Press, New York, pp 343–356Google Scholar
  17. Milloy S, Glick SD (1976) Factors influencing tolerance to d-amphetamine-induced anorexia in rats. Arch Int Pharmacodyn 221:87–95Google Scholar
  18. Samanin R, Ghezzi D, Valzelli L, Garattini S (1972) The effects of selective lesioning of brain serotonin or catecholaminergic containing neurons on the anorectic activity of fenfluramine and amphetamine. Eur J Pharmacol 19:318–322Google Scholar
  19. Schuster CR, Dockens WS, Woods JC (1966) Behavioral variables affecting the development of amphetamine tolerance. Psychopharmacologia 9:170–182Google Scholar
  20. Sofia DR, Barry H (1974) Acute and chronic effects of Δ 9-tetrahydrocannabinol on food intake by rats. Psychopharmacologia 39:213–222Google Scholar
  21. Southgate PJ, Mayer SR, Boxall E, Wilson AB (1971) Some 5-hydroxytryptamine-like actions of fenfluramine: a comparison with (+)-amphetamine and diethylpropion. J Pharm Pharmacol 23:600–605Google Scholar
  22. Taylor M, Goudie AJ, Williams A (1973) The effects of chronic fenfluramine administration on behavior and body weight. Psychopharmacologia 31:63–76Google Scholar
  23. Tormey J, Lasagna L (1960) Relation of thyroid function to acute and chronic effects of amphetamine in the rat. J Pharmacol Exp Ther 128:201–209Google Scholar
  24. Trulson ME, Jacobs BL (1979) Long term amphetamine treatment decreases brain serotonin metabolism: implications for theories of schizophrenia. Science 205:1295–1297Google Scholar
  25. Vesell E, Lang C, White W, Passananti G, Tripp S (1973) Hepatic drug metabolism in rats: impairment in a dirty environment. Science 179:896–897Google Scholar
  26. Weston PF, Overstreet DH (1976) Does tolerance develop to low doses of d- and l-amphetamine on locomotor activity in rats? Pharmacol Biochem Behav 5:645–649Google Scholar
  27. Wiepkema PR (1971) Behavioral factors in the regulation of food intake. Proc Nutr Soc 30:142–149Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • Ronald N. Hunsinger
    • 1
  • T. Bradford Barnes
    • 1
  • John C. Kapeghian
    • 1
  • Marvin C. Wilson
    • 1
  1. 1.Department of Pharmacology, School of PharmacyUniversity of MississippiUniversityUSA

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