Abstract
Rats were trained to self-administer cocaine (0.5 mg/kg/infusion) and were then pretreated with the 5-HT1A agonist 8-OH-DPAT (0.125, 0.25 or 0.5 mg/kg, SC). 8-OH-DPAT pretreatment produced a decrease in reinforced response rates. When the effect of 8-OH-DPAT (0.5 mg/kg, SC) on responding for a range of cocaine doses was assessed, the drug produced a decrease in response rates when lower doses of cocaine served as the reinforcer. Fluoxetine (10 mg/kg, IV), an indirect 5-HT agonist, also reduced reinforced response rates for a low dose infusion of cocaine. Rates of responding for infusions of higher cocaine doses were not affected by fluoxetine pretreatment during an FR1 schedule of reinforcement. When an FR10 schedule of reinforcement was imposed, reinforced response rates for infusions of higher doses of cocaine were also reduced. Thus, under conditions that produce high rates of responding (low dose infusion or high ratio requirements for an infusion) fluoxetine reduced responding. This effect may be due to the effects at the 5-HT1A receptor, since 8-OH-DPAT produced a similar effect on cocaine self-administration. Given that the effects of these 5-HT agonists are observed only when low doses of cocaine serve as the reinforcer or when task demands are high, it is possible that the suppression of responding reflects an effect that is not specific to the reinforcing impact of cocaine. An alternative explanation for these effects incorporates a concept of unit cost/cocaine infusion that allows for direct comparison across studies that employ different reinforcement schedules.
Similar content being viewed by others
References
Benloucif S, Galloway MP (1989) Regulation of dopamine release by serotonin 1a and 1b agonists measured by microdialysis. Soc Neurosci Abstr 15:1313.
Bieger D, Larochelle L, Hornykiewiez O (1972) A model for the quantitative study of central dopaminergic and serotonergic activity. Eur J Pharmacol 18:128–136
Brown ZW, Amit Z, Weeks JR (1976) Simple flow-thru swivel for infusions into unrestrained animals. Pharmacol Biochem Behav 5:363–365
Carroll ME, Lac ST, Ascencio M, Kragh R (1990a) Fluoxetine reduces intravenous cocaine self-administration in rats. Pharmacol Biochem Behav 35:237–244
Carroll ME, Lac ST, Ascencio M, Kragh R (1990b) Intravenous cocaine self-administration in rats is reduced by dietaryl-tryptophan. Psychopharmacology 100:293–300
Costall B, Naylor RJ, Marsden CD, Pycock CJ (1976) Serotonergic modulation of the dopamine response from the nucleus accumbens. J Pharm Pharmacol 28:523–526
Goeders NE, Smith JE (1983) Coritical dopaminergic involvement in cocaine reinforcement. Science 221:773–775
Jenner P, Sheehy M, Marsden CD (1983) Noradrenaline and 5-hydroxytryptamine modulation of brain dopamine function: implication for the treatment of Parkinson's disease. Br J Clini Pharmacol 5 [suppls]:2779–2798
Jones BJ, Costall B, Domeney AM, Kelley ME, Naylor RJ, Oakley NR, Tyers MB (1988) The potential anxiolytic activity of GR38032F, a 5-HT3 receptor antagonist. Br J Pharmacol 93:985–993
Loh EA, Roberts DCS (1990) Break-points on a progressive ratio schedule of reinforced by intravenous cocaine increase following depletion of forebrain serotonin. Psychopharmacology 101:262–266
Peltier R, Schenk S (1991) GR38032F, a serotonin 5-HT3 antagonist, fails to alter cocaine self-administration in rats. Pharmacol Biochem Behav 39:133–136
Porrino MC, Ritz MC, Goodman NL, Sharpe LG, Kuhar MJ, Goldberg SR (1989) Differential effects of the pharmacological manipulation of serotonin systems on cocaine and amphetamine self-administration in rats. Life Sci 45:1529–1535
Roberts DCS, Corcoran ME, Fibiger HC (1977) On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. Pharmacol Biochem Behav 6:615–620
Scheel-Krüger J (1972) Behavioral and biochemical comparison of amphetamine derivatives, cocaine, benztropine and tricyclic antidepressant drugs. Eur J Pharmacol 18:63–73
Spencer Jr DG, Emmett-Oglesby MW (1985) Parallel processing strategies in the application of microcomputers to the behavioral laboratory. Behav Res Methods Instrum 17:294–300
Waldmeier PC, Stula D (1979) Serotonin-dopamine interactions in the nigrostriatal system. Eur J Pharmacol 55:363–373
Weeks JR (1962) Experimental morphine addiction: method for automatic intravenous injections in unrestrained rats. Science 138:143–144
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Peltier, R., Schenk, S. Effects of serotonergic manipulations on cocaine self-administration in rats. Psychopharmacology 110, 390–394 (1993). https://doi.org/10.1007/BF02244643
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244643