Psychopharmacology

, Volume 99, Issue 2, pp 151–155

SCH 23390 blocks drug-conditioned place-preference and place-aversion: anhedonia (lack of reward) or apathy (lack of motivation) after dopamine-receptor blockade?

  • E. Acquas
  • E. Carboni
  • P. Leone
  • G. Di Chiara
Original Investigations

Abstract

The influence of the D1 antagonist SCH 23390 on the motivational properties of rewarding (morphine, nicotine and diazepam) and aversive (naloxone, phencyclidine and picrotoxin) drugs was studied in the rat in a two-compartment place-conditioning paradigm, which included a pre-conditioning test for spontaneous place-preference. The specific D1 dopamine-receptor antagonist SCH 23390 (0.05 mg/kg SC), paired with both compartments or, separately, with the preferred or with the non-preferred compartment, failed to affect the spontaneous unconditioned preference of the animal. Pairing of morphine (1.0 mg/kg SC), nicotine (0.6 mg/kg SC) or diazepam (1.0 mg/kg IP) with the less preferred compartment induced significant preference for that compartment. Pairing of SCH 23390 (0.05 mg/kg SC) with both compartments completely blocked the place-preference induced by morphine, nicotine and diazepam. Naloxone (0.8 mg/kg SC), phencyclidine (2.5 mg/kg SC) or picrotoxin (2.0 mg/kg IP) paired with the preferred compartment elicited place-aversion. Pairing of SCH 23390 (0.05 mg/kg SC) with both compartments abolished also the place-aversion induced by naloxone, phencyclidine and picrotoxin. The results indicate that blockade of dopamine transmission blocks the motivational properties of rewarding as well as aversive stimuli. It is suggested that neuroleptics rather than simply blocking the rewarding impact of positive reinforcers (anhedonia, lack of pleasure) exert a more general influence on conditioned behaviour by blocking the affective impact of negative as well as positive reinforcers (apathy, lack of motivation).

Key words

Dopamine Morphine Nicotine Diazepam Naloxone Phencyclidine Picrotoxin Place-aversion Place-preference SCH 23390 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Baldessarini RJ (1980) Drugs and the treatment of psychiatric disorders. In: Goodman Gilman A, Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics, 6th edn. Mac Millan, New York, pp 395–418Google Scholar
  2. Bardo MT, Miller JS, Neisewander JS (1984) Conditioned place preference with morphine: the effect of extinction training on the reinforcing CR. Pharmacol Biochem Behav 21:545–549Google Scholar
  3. Bardo MT, Neisewander JL, Miller JS (1986) Repeated testing attenuates conditioned place-preference with cocaine. Psychopharmacology 89:239–243Google Scholar
  4. Barr GA, Paredes W, Bridger WH (1985) Place conditioning with morphine and phencyclidine: dose dependent effects. Life Sci 36:363–368Google Scholar
  5. Belmaker RH, Wald D (1977) Haloperidol in normals. Bri J Psychiatry 131:222–223Google Scholar
  6. Bignami G (1978) Effects of neuroleptics, ethanol, hypnotic-sedatives, tranquilizers, narcotics and minor stimulants in aversive paradigms. In: Anisman H, Bignami G (eds) Psychopharmacology of aversively motivated behaviour. Plenum Press, New York, pp 385–402Google Scholar
  7. Blander A, Hunt T, Blair R, Amit Z (1984) Conditioned place preference: an evaluation of morphine's positive reinforcing properties. Psychopharmacology 84:124–127Google Scholar
  8. Benninger RJ, Cheng M, Hahn BL, Hoffman DC, Mazurski EJ, Morency MA, Ramm P, Stewart RJ (1987) Effects of extinction, pimozide, SCH 23390, and metoclopramide on food-rewarded operant responding of rats. Psychopharmacology 92:343–349Google Scholar
  9. Bozarth MA, Wise RA (1981) Heroin reward is dependent on a dopaminergic substrate. Life Sci 29:1881–1886Google Scholar
  10. Clarke PBS, Fibiger NC (1987) Apparent absence of nicotine-induced conditioned place-preference in rats. Psychopharmacology 92:84–88Google Scholar
  11. Delay J, Deniker P (1952) Io Congrès des Al et Neurol de Langue Fr. In: Compte rendu du Congrès. Masson et Cie, ParisGoogle Scholar
  12. Dews PB, Morse WH (1961) Behavioural pharmacology. Ann Rev Pharmacol 1:145–174Google Scholar
  13. Di Chiara G, Imperato A (1986) Preferential stimulation of dopamine release in the nucleus accumbens by opiates, alcohol, and barbiturates: studies with trans-cerebral dialysis in freely moving rats. Ann NY Acad Sci 473:367–381Google Scholar
  14. Di Chiara G, Imperato A (1988a) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85:5274–5278Google Scholar
  15. Di Chiara G, Imperato A (1988b) Opposite effects of μ and kopiate agonists on dopamine-release in the nucleus accumbens and in the dorsal caudate of freely moving rats. J Pharmacol Exp Ther 244:1067Google Scholar
  16. Di Chiara G, Imperato A, Mulas A (1987) Preferential stimulation of dopamine release in the mesolimbic system: a common feature of drugs of abuse. In: M. Sandler et al. (eds) Neurotransmitter interactions in the basal ganglia. Raven Press, New York, pp 171–182Google Scholar
  17. Fudala PJ, Teoh KW, Iwamoto ET (1985) Pharmacologic characterization of nicotine-induced conditioned place preference. Pharmacol Biochem Behav 22:237–241Google Scholar
  18. Garcia J, Kimeldorf DJ, Hunt EL (1957) Spatial avoidance in the rat as a result of exposure to ionizing radiation. Br J Radiat 30:318–321Google Scholar
  19. Grilly DM, Johnson SK, Minardo R, Jacoby D, LaRiccia J (1984) How do tranquilizing agents selectively inhibit conditioned avoidance responding? Psychopharmacology 84:262–267Google Scholar
  20. Hyttel J (1983) SCH 23390 the first selective dopamine D1 antagonist. Eur J Pharmacol 91:153Google Scholar
  21. Imperato A, Di Chiara G (1986) Preferential stimulation of dopamine-release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther 239:219–228Google Scholar
  22. Imperato A, Mulas A, Di Chiara G (1986) Nicotine preferentially stimulates dopamine release in the limbic system of freely moving rats. Eur J Pharmacol 132:337Google Scholar
  23. Iorio LC, Barnett A, Leitz FH, Houser VP, Korduba CA (1983) SCH 23390, a potential benzazepine antipsycotic with unique interactions on dopaminergic systems. J Pharmacol Exp Ther 226:462Google Scholar
  24. Iwamoto ET (1986) Place-aversion conditioned by phencyclidine in rats: development of tolerance and pharmacologic antagonism. Alcohol Drugs Res 6:265–276Google Scholar
  25. Katz RJ, Gormezano G (1979) A rapid and inexpensive technique for assessing the reinforcing effects of opiate drugs. Pharmacol Biochem Behav 11:231–233Google Scholar
  26. Koob GF, Le HT, Creese I (1987) The D1 dopamine receptor antagonist SCH 23390 increases cocaine self-administration in rat. Neurosci Lett 79:315–320Google Scholar
  27. Leone P, Di Chiara G (1987) Blockade of D-1 receptors by SCH 23390 antagonizes morphine- and amphetamine-induced place preference conditioning. Eur J Pharmacol 135:251Google Scholar
  28. Liebman JM (1983) Discriminating between reward and performance: a critical review of intracranial self-stimulation methodology. Neurosci Biobehav Rev 7:45–72Google Scholar
  29. Mackey WB, Van der Kooy D (1984) Neuroleptics block the positive reinforcing effects of amphetamine but not of morphine as measured by place conditioning. Pharmacol Biochem Behav 22:101–105Google Scholar
  30. Mackintosh NJ (1974) A theory of attention: variation on the associability of stimuli with reinforcement. The psychology of animal learning. Academic Press, LondonGoogle Scholar
  31. Martin-Iversen MT, Ortman R, Fibiger HC (1984) Place preference conditioning with methylphenidate and nomifensine. Brain Res 332:59–67Google Scholar
  32. Mucha RF, Iversen SD (1984) Reinforcing properties of morphine and naloxone revealed by conditioned place preference: a procedural examination. Psychopharmacology 82:241–247Google Scholar
  33. Mucha RF, Van der Kooy D, O'Shaughnessy M, Bucenieks P (1982) Drug reinforcement studied by the use of place conditioning in rat. Brain Res 243:91–105Google Scholar
  34. Nakajima S (1986) Suppression of operant responding in the rat by dopamine D1 receptor blockade with SCH 23390. Physiology 14:111–114Google Scholar
  35. Nakajima S, MacKenzie GM (1986) Reduction of the rewarding effect of brain stimultion by blockade of dopamine D1 receptor with SCH 23390. Pharmacol Biochem Behav 24:919–923Google Scholar
  36. Reicher MA, Holman EW (1977) Location preference and flavor aversion reinforced by amphetamine in rats. Anim Learn Behav 5:343–346Google Scholar
  37. Rossi NA, Reid LD (1976) Affective states associated with morphine injections. Physiol Psychol 4:269–274Google Scholar
  38. Sanger DJ (1987) The actions of SCH 23390, a D1 receptor antagonist, on operant and avoidance behavior in rats. Pharmacol Biochem Behav 26:509–513Google Scholar
  39. Sherman JE, Pickman C, Rice A, Liebeskind JC, Holman EW (1980) Rewarding and aversive effects of morphine: temporal and pharmacological properties. Pharmacol Biochem Behav 13:501–505Google Scholar
  40. Spyraki C, Fibiger HC, Phillips AG (1982a) Dopaminergic substrates of amphetamine-induced place preference conditioning. Brain Res 253:185–193Google Scholar
  41. Spyraki C, Fibiger HC, Phillips AG (1982b) Cocaine-induced place preference conditioning: lack of effects of neuroleptics and 6-hydroxydopamine lesions. Brain Res 253:195–203Google Scholar
  42. Spyraki C, Fibiger HC, Phillips AG (1983) Attenuation of heroin reward in rats by disruption of the mesolimbic dopamine system. Psychopharmacology 79:278–283Google Scholar
  43. Spyraki C, Kazandjian A, Varonos D (1985) Diazepam-induced place preference conditioning: appetitive and antiaversive properties. Psychopharmacology 87:225–232Google Scholar
  44. Wise RA (1983) Neuroleptics and operant behavior: the anhedonia hypothesis. Behav Brain Sci 5:39–53Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • E. Acquas
    • 1
  • E. Carboni
    • 1
  • P. Leone
    • 1
  • G. Di Chiara
    • 1
  1. 1.Institute of Experimental Pharmacology and ToxicologyUniversity of CagliariCagliariItaly

Personalised recommendations