, Volume 101, Issue 2, pp 262–266

Break-points on a progressive ratio schedule reinforced by intravenous cocaine increase following depletion of forebrain serotonin

  • Elliot A. Loh
  • David C. S. Roberts
Original Investigations


The effect of intracerebral injections of 5,7-dihydroxy-tryptamine (5,7-DHT) on cocaine self-administration behavior was assessed. Rats were tested on a progressive ratio (PR) schedule for cocaine reinforcement. The first response on the lever each day produced an IV infusion of cocaine (0.6 mg/injection) after which the requirements of the schedule escalated with each reinforcement until the behavior extinguished. The final ratio completed was defined as the breaking point. Bilateral injections of 5,7-DHT into either the medial forebrain bundle (MFB) or amygdala (AMY) significantly increased the breaking points on the PR schedule compared to vehicle-injected control animals. We interpret these data to indicate that depletion of forebrain serotonin increases the incentive value of cocaine.

Key words

Amygdala Cocaine 5,7-Dihydroxy-tryptamine Median forebrain bundle Self-administration Serotonin 


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  1. Azzaro AJ, Rutledge CO (1973) Selectivity of release of norepinephrine, dopamine, and 5-hydroxytryptamine by amphetamine in various regions of the rat brain. Biochem Pharmacol 22:2801–2813Google Scholar
  2. Chow HL, Beck CHM (1984)p-Chlorophenylalanine andp-chloroamphetamine pretreatment of apomorphine-challenged rats: effect on solitary and social behavior. Eur J Pharmacol 102:297–304Google Scholar
  3. Deminiere JM, Simon H, Herman JP, Le Moal M (1984) 6-Hydroxydopamine lesions of the dopamine mesocorticolimbic cell bodies increases (+)-amphetamine self-administration. Psychopharmacology 83:281–284Google Scholar
  4. Deminiere JM, Taghzouti K, Le Moal M, Simon H (1987) Increased sensitivity to amphetamine and facilitation of amphetamine self-administration after 6-hydroxydopamine lesions of the amygdala. Psychopharmacology 94:232–236Google Scholar
  5. Hodos W (1961) Progressive ratio as a measure of reward strength. Science 134:943–944Google Scholar
  6. Koob GF, Le HT, Creese I (1987) The D1 dopamine receptor antagonist SCH 23390 increases cocaine self-administration in the rat. Neurosci Lett 79:315–320Google Scholar
  7. Korsgaard S, Gerlach J, Christensson E (1985) Behavioral aspects of serotonin-dopamine interactions in the monkey. Eur J Pharmacol 118:245–252Google Scholar
  8. Leccese AP, Lyness WH (1984) The effects of the putative 5-hydroxytryptamine receptor active agents ond-amphetamine self-administration in controls and rats with 5,7-dihydroxytryptamine median forebrain bundle lesions. Brain Res 303:153–162Google Scholar
  9. Lyness WH, Moore KE (1983) Increased self-administration ofd-amphetamine by rats pretreated with metergoline. Pharmacol Biochem Behav 18:721–724Google Scholar
  10. Lyness WH, Friedle NM, Moore KE (1979) Destruction of dopaminergic nerve terminals in nucleus accumbens: effect ond-amphetamine self-administration. Pharmacol Biochem Behav 11:553–556Google Scholar
  11. Lyness WH, Friedle NM, Moore KE (1980) Increased self-administration ofd-amphetamine after destruction of 5-hydroxytryptaminergic neurons. Pharmacol Biochem Behav 12:937–941Google Scholar
  12. Mefford IN (1981) Application of high performance liquid chromatography with electrochemical detection to neurochemical analysis: measurement of catecholamines, serotonin and metabolites the rat brain. J Neurosci Methods 3:207–224Google Scholar
  13. Pettit HO, Ettenburg A, Bloom FE, Koob GF (1984) Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration. Psychopharmacology 84:167–173Google Scholar
  14. Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ (1987) Cocaine receptors on dopamine transporters are related to the self-administration of cocaine. Science 237:1219–1223Google Scholar
  15. Roberts DCS (1989a) Breaking points on a progressive ratio schedule reinforced by intravenous apomorphine increase daily following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 32:43–47Google Scholar
  16. Roberts DCS (1989b) Neural substrates mediating cocaine reinforcement: monoamine systems. In: Lakoski JM, Gallaway MP, White FJ (eds) Cocaine: pharmacology, physiology and clinical strategies. The Telford Press, Caldwell (in press)Google Scholar
  17. Roberts DCS, Goeders N (1989) Drug self-administration: experimental methods and determinants. In: Boulton AA, Baker GB, Greenshaw AJ (eds) Neuromethods, vol. 13, Psychopharmacology 1: Psychopharmacology. Humana Press, Clifton, New Jersey (in press)Google Scholar
  18. Roberts DCS, Vickers G (1984) Atypical neuroleptics increase self-administration of cocaine: an evaluation of a behavioural screen for antipsychotic activity. Psychopharmacology 82:135–139Google Scholar
  19. Roberts DCS, Corcoran ME, Fibiger HC (1977) On the role of ascending catecholamine systems in self-administration of cocaine. Pharmacol Biochem Behav 6:615–620Google Scholar
  20. Roberts DCS, Koob GF, Klonoff P, Fibiger HC (1980) Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 12:781–787Google Scholar
  21. Roberts DCS, Bennett SAL, Vickers G (1989a) The estrous cycle affects cocaine self-administration on a progressive ratio schedule in rats. Psychopharmacology 98:408–411Google Scholar
  22. Roberts DCS, Loh EA, Vickers G (1989b) Self-administration of cocaine on a progressive ratio schedule in rats: dose-response relationship and effect of haloperidol pretreatment. Psychopharmacology 97:535–538Google Scholar
  23. Scheel-Krüger J (1972) Behavioral and biochemical comparison of amphetamine derivatives, cocaine, benztropine and tricyclic anti-depressant drugs. Eur J Pharmacol 18:63–73Google Scholar
  24. Smith FL, Yu DSL, Smith DG, Leccese AP, Lyness WH (1986) Dietary tryptophan supplements attenuate amphetamine self-administration in the rat. Pharmacol Biochem Behav 25:849–854Google Scholar
  25. Wilson MC, Schuster CR (1973) Cholinergic influence on intravenous cocaine self-administration in the rhesus monkey. Pharmacol Biochem Behav 1:643–649Google Scholar
  26. Yokel RA, Wise RA (1976) Attenuation of intravenous amphetamine reinforcement by central dopamine blockade in rats. Psychopharmacology 48:311–318Google Scholar
  27. Zito KA, Vickers G, Roberts DCS (1985) Disruption of cocaine and heroin self-administration following kainic acid lesions of the nucleus accumbens. Pharmacol Biochem Behav 23:1029–1036Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Elliot A. Loh
    • 1
  • David C. S. Roberts
    • 1
  1. 1.Department of PsychologyCarleton UniversityOttawaCanada

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