, Volume 105, Issue 3, pp 329–334 | Cite as

Facilitation and inhibition of feeding by a single dose of amphetamine: relationship to baseline intake and accumbens cholecystokinin

  • Terrence L. Sills
  • Franco J. Vaccarino
Original Investigations


Amphetamine (AMP) administered in high doses suppresses feeding. However, in low doses AMP has been shown to both suppress and facilitate feeding. Further, there is some indication of individual differences in the feeding response to low doses of AMP. Evidence indicates that AMP's effects on feeding are dopamine-mediated and that the nucleus accumbens (Acb) may be an important site of action. Of interest here is the fact that CCK terminals exist within the Acb and CCK modulates DA activity. Experiment 1 investigated the effects of intra-Acb CCK administration as a function of individual differences in the feeding response to a low dose of systemic AMP. Results indicate that response to AMP was baseline dependent. AMP stimulated feeding in low baseline feeders and suppressed feeding in high baseline feeders. Intra-Acb CCK blocked the AMP-induced increase in feeding but not the AMP-induced anorexia. In experiment 2, the effects of intra-Acb CCK administration on baseline feeding were assessed. Intra-Acb CCK suppressed baseline feeding, but only when there was a high level of intake. It is speculated that Acb-DAergic activity may play a role in the observed feeding effects of both AMP and CCK.

Key words

Amphetamine Cholecystokinin Nucleus accumbens Feeding Anorexia Sugar Individual differences Baseline dependent Rat 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Blaha CD, Lane RF, Phillips AG (1987a) Application of in vivo electro-chemistry to cholecystokinin-dopamine interactions in the ventral striatum. In: Carpenter MB, Jayaraman A (eds) The basal ganglia II. Plenum Press, New York, pp 115–142Google Scholar
  2. Blaha CD, Phillips AG, Lane RF (1987b) Reversal by cholecystokinin of apomorphine-induced inhibition of dopamine release in the nucleus accumbens of the rat. Regul Pept 17:301–310Google Scholar
  3. Blundell JE, Latham CJ (1980) Characterisation of adjustments to the structure of feeding behaviour following pharmacological treatment: effects of amphetamine and fenfluramine and the antagonism produced by pimozide and methergoline. Pharmacol Biochem Behav 12:717–722Google Scholar
  4. Carr GD, White NM (1986) Contributions of dopamine terminal areas to amphetamine-induced anorexia and adipsia. Pharmacol Biochem Behav 25:1–6Google Scholar
  5. Colle LM, Wise RA (1988) Facilitory and inhibitory effects of nucleus accumbens amphetamine on feeding. Ann NY Acad Sci 537:491–492Google Scholar
  6. Crawley JN (1988) Modulation of mesolimbic dopaminergic behaviors by cholecystokinin. Ann NY Acad Sci 537:380–396Google Scholar
  7. De Witte P, Swanet E, Gewiss M, Golman S, Roques B, Vanderhaeghen JJ (1985) Psychopharmacological profile of cholecystokinin using the self-stimulation and the drug discrimination paradigms. Ann NY Acad Sci 448:470–487Google Scholar
  8. Dobrzanski S, Doggett NS (1976) The effects of (+)-amphetamine and fenfluramine on feeding in starved and satiated mice. Psychopharmacology 48:283–286Google Scholar
  9. Eichler AJ, Antelman SM (1977) Apomorphine: feeding or anorexia depending on internal state. Commun Psychopharmacol 1:533–540Google Scholar
  10. Emson PC, Lee CM, Rehfeld JF (1980) Cholecystokinin octapeptide: vesicular localization and calcium dependent release from rat brain in vivo. Life Sci 26:2157–2163Google Scholar
  11. Evans KR, Eikelboom R (1987) Feeding induced by ventricular bromocriptine and amphetamine: a possible excitatory role for dopamine in eating behavior. Behav Neurosci 101 [4]:591–593Google Scholar
  12. Evans KR, Vaccarino FJ (1986) Intra-nucleus accumbens amphetamine: dose-dependent effects on food intake. Pharmacol Biochem Behav 25:1149–1151Google Scholar
  13. Evans KR, Vaccarino FJ (1987) Effects ofd- andl-amphetamine on food intake: evidence for a dopaminergic substrate. Pharmacol Biochem Behav 27:649–652Google Scholar
  14. Evans KR, Vaccarino FJ (1990) Amphetamine- and morphine-induced feeding: evidence for involvement of reward mechanisms. Neurosci Biobehav Rev 14:9–22Google Scholar
  15. Gilbert DB, Cooper SJ (1985) Analysis of dopamine D1 and D2 receptor involvement ind- andl-amphetamine-induced anorexia in rats. Brain Res Bull 15:385–389Google Scholar
  16. Glick SD, Muller RU (1971) Paradoxical effects of low doses ofd-amphetamine in rats. Psychopharmacologia 22:396–402Google Scholar
  17. Golterman NR, Stengaard-Pedersen H, Rehfeld JF, Christensen NJ (1981) Newly synthesized cholecystokinin in subcellular fractions of rat brain. J Neurochem 36:859–865Google Scholar
  18. Grinker JA, Drewnowski A, Enns M, Kisseleff H (1980) The effects ofd-amphetamine and fenfluramine on feeding patterns and activity of obese and lean Zucker rats. Pharmacol Biochem Behav 12:265–275Google Scholar
  19. Heffner TG, Zigmond MJ, Stricker EM (1977) Effects of dopaminergic agonists and antagonists on feeding in intact and 6-hydroxydopamine-treated rats. J Pharmacol Exp Ther 201:386–399Google Scholar
  20. Hokfelt T, Skirboll L, Rehfeld JF, Goldstein M, Markey K, Dann O (1980) A subpopulation of mesencephalic dopamine neurons projecting to limbic areas contain a cholecystokinin-like peptide: evidence from immunohistochemistry combined with tracing. Neuroscience 5:2093–2124Google Scholar
  21. Holtzman SG (1974) Behavioral effects of separate and combined administration of naloxone andd-amphetamine. J Pharmacol Exp Ther 189:51–60Google Scholar
  22. Kelley AE, Gauthier AM, Lang CG (1989) Amphetamine microinjections into distinct striatal subregions cause dissociable effects on motor and ingestive behavior. Behav Brain Res 35:27–39Google Scholar
  23. Leibowitz SF (1973) Brain norepinephrine and ingestive behaviour. In: Usdin E, Snyder SH (eds) Frontiers in cathecholamine research. Pergamon Press, New York, pp 711–713Google Scholar
  24. Leibowitz SF (1975a) Amphetamine: possible site and mode of action for producing anorexia in the rat. Brain Res 84:160–167Google Scholar
  25. Leibowitz SF (1975b) Catecholaminergic mechanisms of the lateral hypothalamus: their role in the mediation of amphetamine anorexia. Brain Res 98:529–545Google Scholar
  26. Leibowitz SF (1978) Paraventricular nucleus: a primary site mediating adrenergic stimulation of feeding and drinking. Pharmacol Biochem Behav 8:163–175Google Scholar
  27. Leibowitz SF (1986) Brain monoamines and peptides: role in the control of eating behavior. Fed Proc 45:1396–1403Google Scholar
  28. Lewander T (1977) Effects of amphetamine in animals. In: Martin WR (ed) Drug addiction II. Springer-Verlag, New York, pp 33–246Google Scholar
  29. Moran TH, Robinson PH, Goldrich MS, McHugh PR (1986) Two brain cholecystokinin receptors: implications for behavioral actions. Brain Res 362:175–179Google Scholar
  30. Orthen-Gambill N (1985) Sucrose intake unaffected by fenfluramine but suppressed by amphetamine administration. Psychopharmacology 87:25–29Google Scholar
  31. Paxinos G, Watson C (1982) The rat brain in stereotaxic atlas. Academic Press, New YorkGoogle Scholar
  32. Robbins T (1981) Behavioural determinants of drug action: rate-dependency revisited. In: Cooper SJ (ed) Theory in psychopharmacology, vol 1. Academic Press, London, pp 1–63Google Scholar
  33. Ruggeri M, Ungerstedt U, Agnati LF, Mutt V, Harfstrand A, Fuxe K (1987) Effects of cholecystokinin peptides and neurotensin on dopamine release and metabolism in the rostral and caudal part of the nucleus accumbens using intracerebral dialysis in the anaesthetized rat. Neurochem Int 10:509–520Google Scholar
  34. Schneider LH, Alpert JE, Iversen SD (1983) CCK-8 modulation of mesolimbic dopamine: antagonism of amphetamine-stimulated behaviors. Peptides 4:749–753Google Scholar
  35. Skirboll LR, Grace AA, Hommer DW, Rehfeld J, Goldstein M, Hokfelt T, Bunney BS (1981) Peptide-monoamine coexistence: studies of the action of cholecystokinin-like peptide on the electrical activity of midbrain dopamine neurons. Neuroscience 6:2111–2124Google Scholar
  36. Vaccarino FJ, Koob GF (1984) Microinjections of nanogram amounts of sulfated cholecystokinin octapeptide into the rat nucleus accumbens attenuates brain stimulation reward. Neurosci Lett 52:61–66Google Scholar
  37. Vaccarino FJ, Rankin J (1989) Nucleus accumbens cholecystokinin (CCK) can either attenuate or potentiate amphetamine-induced locomotor activity: evidence for rostral-caudal differences in accumbens CCK function. Behav Neurosci 4:831–836Google Scholar
  38. Van Ree JM, Gaffori O, De Wied D (1983) In rats, the behavioral profile of CCK-8 related peptides resembles that of antipsychotic agents. Eur J Pharmacol 93:63–78Google Scholar
  39. Vickroy TW, Bianchi BR (1989) Pharmacological and mechanistic studies of cholecystokinin-facilitated [3H] dopamine efflux from rat nucleus accumbens. Neuropeptides 13:43–50Google Scholar
  40. Wang RY, Hu XT (1986) Does cholecystokinin potentiate dopamine action in the nucleus accumbens? Brain Pes 380:363–367Google Scholar
  41. Weiss F, Tanzer DJ, Ettenberg A (1988) Opposite actions of CCK-8 on amphetamine-induced hyperlocomotion and stereotypy following intracerebroventricular and intra-accumbens injections in rats. Pharmacol Biochem Behav 30:309–317Google Scholar
  42. White FJ, Wang RY (1984) Interactions of cholecystokinin octapeptide and dopamine on nucleus accumbens neurons. Brain Res 300:161–166Google Scholar
  43. Winn P, Williams SF, Herberg LJ (1982) Feeding stimulated by very low doses ofd-amphetamine administered systemically or by microinjection into the striatum. Psychopharmacology 78:336–341Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Terrence L. Sills
    • 1
  • Franco J. Vaccarino
    • 1
  1. 1.Psychology DepartmentUniversity of TorontoTorontoCanada

Personalised recommendations