Psychopharmacology

, Volume 87, Issue 3, pp 328–333 | Cite as

The puzzle of drug-induced conditioned taste aversion: Comparative studies with cathinone and amphetamine

  • A. J. Goudie
  • T. Newton
Original Investigations

Abstract

The potency of dl-cathinone (the active constituent of the Khat plant) was compared with that of d-amphetamine in the conditioned taste aversion (C. T. A.) procedure and in a test of drug-induced adipsia in rats. Both drugs induced C.T.A., the potency ratio being 1∶17 (amphetamine was more potent). Both drugs induced adipsia in deprived rats given access to water for 120 min. The potency ratio in this procedure was 1∶4. Potency in the C.T.A. procedure did not therefore correlate with potency in inducing adipsia; consequently drug-induced C.T.A. cannot be attributed to conditioned adipsia. In the adipsia test the drugs had similar durations of action, thus factors related to duration of drug action (cf Cappell and Le Blanc 1977) cannot account for the surprisingly low potency of cathinone in the C.T.A. procedure. These data, obtained with stimulant drugs with similar structures and similar actions in a variety of conventional in vivo and in vitro pharmacological tests, illustrate the unpredictable nature of drug actions in the C.T.A. procedure. The low potency of cathinone in inducing C.T.A. could not be predicted from knowledge of the potency of this compound in tests of adipsia (as shown here) or (as reported elsewhere) in tests of anorexia, locomotor stimulation, stereotypy, suppression of operant responding, drug discrimination, release and inhibition of reuptake of dopamine and noradrenaline, lethality and actions on the cardiovascular system. All of these studies have reported potency ratios considerably lower than 1∶17, which were nevertheless similar to the 1∶4 ratio observed in the adipsia test. It is suggested that the weak potency of cathinone in the C.T.A. procedure may be related to its comparatively potent reinforcing actions in the self-administration procedure.

Key words

Khat Cathinone Amphetamine Conditioned taste aversion Adipsia Toxicity Self-administration Rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Booth DA, D'Mello GD, Pilcher CWT, Stolerman IP (1977) Comparative potencies of amphetamine, fenfluramine and related compounds in taste aversion experiments in rats. Br J Pharmacol 61:669–677Google Scholar
  2. Cappell HD, Le Blanc AE (1977) Gustatory avoidance conditioning by drugs of abuse: Relationships to general issues in research on drug dependence. In: Milgram NW, Krames L, Alloway TM (eds) Food aversion learning. New York, Plenum Press, pp 133–167Google Scholar
  3. Carey RJ (1978) A comparison of food intake suppression produced by giving amphetamine as an aversion treatment versus as an anorexic treatment. Psychopharmacology 56:45–48Google Scholar
  4. De La Garza R, Johanson CE (1983) The discriminative stimulus properties of cocaine in the rhesus monkey. Pharmacol Biochem Behav 19:145–148Google Scholar
  5. D'Mello GD, Stolerman IP, Booth DA, Pilcher CWT (1977) Factors affecting flavour aversions conditioned with amphetamine in rats. Pharmacol Biochem Behav 7:185–190Google Scholar
  6. D'Mello GD, Goldberg DM, Goldberg SR, Stolerman IP (1981) Conditioned taste aversion and operant behaviour in rats. Effects of cocaine and some long acting derivatives. J Pharmacol Exp Ther 219:60–68Google Scholar
  7. Domjan M, Foster K, Gillian DJ (1981) Effects of distribution of the drug unconditioned stimulus on taste-aversion learning. Physiol Behav 14:907–909Google Scholar
  8. Foltin RW, Schuster CR (1981) The effects of dl-cathinone in a gustatory avoidance paradigm. Pharmacol Biochem Behav 14:907–909Google Scholar
  9. Foltin RW, Schuster CR (1982a) Behavioural tolerance and cross tolerance to dl-cathinone and d-amphetamine in rats. J Pharmacol Exp Ther 222:126–131Google Scholar
  10. Foltin RW, Schuster CR (1982b) The effects of cocaine in a gustatory avoidance paradigm: A procedural analysis. Pharmacol Biochem Behav 16:347–352Google Scholar
  11. Foltin RW, Schuster CR (1983) Interaction between the effects of intragastric meals and drugs on feeding in rhesus monkeys. J Pharmacol Exp Ther 226:405–410Google Scholar
  12. Foltin RW, Woolverton WL, Schuster CR (1983) Effects of psychomotor stimulants, alone and in pairs, on milk drinking in the rat after intraperitoneal and intragastric administration. J Pharmacol Exp Ther 226:411–418Google Scholar
  13. Glennon RA, Showalter DA (1981) The effect of cathinone and several related derivatives on locomotor activity. Res Commun Substance Abuse 2:186–191Google Scholar
  14. Goudie AJ, Thornton EW (1977) Role of drug metabolism in the aversive properties of d-amphetamine. I.R.C.S. Medical Science 5:93Google Scholar
  15. Goudie AJ, Dickins DW, Thornton EW (1978) Cocaine-induced conditioned taste aversion in rats. Pharmacol Biochem Behav 8:757–761Google Scholar
  16. Goudie AJ, Dickins DW (1978) Nitrous oxide-induced conditioned taste aversion in rats: The role of duration of drug administration and its relation to the taste aversion/self-administration “paradox”. Pharmacol Biochem Behav 9:587–592Google Scholar
  17. Goudie AJ (1979) Aversive stimulus properties of drugs. Neuropharmacology 18:971–979Google Scholar
  18. Goudie AJ (1985a) Aversive stimulus properties of drugs: The conditioned taste aversion paradigm. In: Greenshaw AJ, Dourish CT (eds) Experimental approach in psychopharmacology, Humana Press Inc, New Jersey (in press)Google Scholar
  19. Goudie AJ (1985b) Comparative effects of cathinone and amphetamine on operant behaviour in rats: A rate-dependency analysis. Pharmacol Biochem Behav (in press)Google Scholar
  20. Goudie AJ, Newton T, Atkinson J, Demellweek C (1984) Discriminative and aversive actions of dl-cathinone and d-amphetamine in rats: Comparison with effects on operant responding. Psychopharmacology 83:S3Google Scholar
  21. Greenshaw AJ, Dourish CT (1984a) Differential aversive stimulus properties of beta-phenylethylamine and of d-amphetamine. Psychopharmacology 82:189–193Google Scholar
  22. Greenshaw AJ, Dourish CT (1984b) Beta-phenylethylamine and d-amphetamine: Differential potency in the conditioned taste aversion paradigm. In: Boulton A, Baker G, Dewhurst W, Sandler M (eds) Neurobiology of the trace amines. Humana Press Inc, New JerseyGoogle Scholar
  23. Grote FW, Brown RT (1971) Conditioned taste aversions: Two-stimulus tests are more sensitive than one-stimulus tests. Behav Res Methods Instrum 3:311–312Google Scholar
  24. Hallbach H (1972) Medical aspects of the chewing of Khat leaves. Bulletin of World Health Organization 47:21–29Google Scholar
  25. Huang D, Wilson MC (1983) The role of dopaminergic and serotonergic systems in the acute lethal effects of dl-cathinone, d-amphetamine and cocaine in mice: A comparative study. Res Commun Substance Abuse 4:215–225Google Scholar
  26. Johanson CE, Schuster CR (1981) A comparison of the behavioural effects of l- and dl-cathinone and d-amphetamine. J Pharmacol Exp Ther 219:355–362Google Scholar
  27. Kalix P (1980a) Hypermotility of the amphetamine type produced by a constituent of Khat leaves. Br J Pharmacol 68:11–13Google Scholar
  28. Kalix P (1980b) A constituent of Khat leaves with amphetamine-like releasing properties. Eur J Pharmacol 68:213–215Google Scholar
  29. Kalix P (1981) Cathinone, an alkaloid from Khat leaves with an amphetamine-like releasing effect. Psychopharmacology 74:269–270Google Scholar
  30. Kalix P (1982) The amphetamine-like releasing effect of the alkaloid (-) cathinone on rat nucleus accumbens and rabbit caudate nucleus. Prog Neuro-Psychopharmacol Biol Psychiatr 6:43–49Google Scholar
  31. Kalix P (1983a) A comparison of the catecholamine-releasing effect of the Khat alkaloids (-) cathinone and (+) norpseudoephedrine. Drug Alcohol Dependence 11:395–401Google Scholar
  32. Kalix P (1983b) Effect of the alkaloid (-) cathinone on the release of radioactivity from rabbit atria prelabelled with 3H-norepinephrine. Life Sci 32:801–807Google Scholar
  33. Kalix P (1984a) The pharmacology of Khat. Gen Pharmacol 15:179–187Google Scholar
  34. Kalix P (1984b) Effect of the alkaloid (-)-cathinone on the release of radioactivity from rat striatal tissue prelabelled with 3H-serotonin. Neuropsychobiology 12:127–129Google Scholar
  35. Khan I, Kalix P (1984) Khat, a plant with amphetamine-like releasing properties. TIPS 5:326–328Google Scholar
  36. Kohli JD, Goldberg LI (1982) Cardiovascular effects of (-)-cathinone in the anaesthetized dog: Comparison with (+)-amphetamine. J Pharm Pharmacol 34:338–340Google Scholar
  37. Krikorian AD (1983) Khat and its use: An historical perspective. In: Shahandeh B (ed) The health and socio-economic aspects of Khat use. International Council on Alcohol and Addiction, Lausanne, pp 7–71Google Scholar
  38. Riley AL, Tuck D (1985) Conditioned taste aversions: An index of toxicity. Annals New York Acad Sci (in press)Google Scholar
  39. Schechter MD, Rosecrans JA, Glennon RA (1984) Comparison of behavioural effects of cathinone, amphetamine and apomorphine. Pharmacol Biochem Behav 20:181–184Google Scholar
  40. Stolerman IP, D'Mello GD (1978) Amphetamine-induced hypodipsia and its implications for conditioned taste aversion in rats. Pharmacol Biochem Behav 8:333–338Google Scholar
  41. Stolerman IP, D'Mello GD (1981) Oral self-administration and the relevance of conditioned taste aversions. In: Thompson T, Dews PB, McKim WA (eds) Advances in behavioural pharmacology, Vol 3. Academic Press, New York, pp 169–214Google Scholar
  42. Switzman L, Hunt T, Amit Z (1981) Heroin and morphine: Aversive and analgesic effects in rats. Pharmacol Biochem Behav 15:755–759Google Scholar
  43. Szendrei K (1983) Recent progress in Khat chemistry. In: Shahandeh B (ed) The health and socio-economic aspects of Khat use. International Council on Alcohol and Addictions. Lausanne, pp 91–109Google Scholar
  44. Woolverton WL, Johanson CE (1984) Preference in rhesus monkeys given a choice between cocaine and dl-cathinone. J Exp Anal Behav 41:35–43Google Scholar
  45. Zelger JL, Schorno HX, Carlini EA (1979) Behavioral effects of cathinone, an amine obtained from Catha edulis Forsk: Comparisons with amphetamine, norpseudoephedrine, apomorphine and nomifensine. Bull Narc 32:67–81Google Scholar
  46. Zelger JL, Carlini EA (1980) Anorexigenic effects of two amines obtained from Catha edulis Forsk. (Khat) in rats. Pharmacol Biochem Behav 12:701–705Google Scholar
  47. Zelger JL, Carlini EA (1981) Influence of cathinone (α-Aminopropiophenone) and cathine (phenylpropanolamine) on circling behaviour and on the uptake and release of [3H]dopamine in striatal slices of rats. Neuropharmacology 20:839–843Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • A. J. Goudie
    • 1
  • T. Newton
    • 1
  1. 1.Department of PsychologyThe University of LiverpoolLiverpoolUK

Personalised recommendations