Abstract
Rationale
Previous studies show that selective serotonin reuptake inhibitors (SSRIs), including fluvoxamine, have a greater effect on ethanol-maintained responding compared with an alternative reinforcer. However, none of these studies matched baseline responding for reinforcers. Because behavioral effects of many drugs depend on the baseline response rate, the preferential effects of SSRIs may be due to different baseline response rates.
Objectives
Fluvoxamine effects on ethanol- and food-maintained responding were compared using a multiple schedule of behavior, providing matched baseline responding and allowing within-subject analysis in two strains of rats.
Methods
The multiple schedule consisted of three consecutive 5-min, fixed-ratio five components (Food1, Ethanol, Food2). Fluvoxamine (3–30 mg/kg, i.p.) was administered 30 min presession. In Lewis rats, fluvoxamine effects were determined at several available ethanol concentrations [8, 16, 32, and 8% (w/v) redetermination]. In Sprague–Dawley rats, fluvoxamine effects were determined when the available ethanol concentration was 8% (w/v).
Results
Baseline responding was stable and well matched under all conditions except 32% ethanol, when responding for ethanol was lower than for food. After the administration of 17.8 mg/kg fluvoxamine, ethanol-maintained responding was 15–33% lower than food-maintained responding in four of the five conditions tested. Breath ethanol assessments indicated that rats had blood ethanol levels of 33 mg/dl following responding for 8% ethanol.
Conclusions
These results are in agreement with previous findings that SSRIs preferentially reduce ethanol-maintained responding and suggest this is not likely due to different baseline levels of responding between the comparison conditions. Further, these results support the hypothesis that alteration of synaptic serotonin can modulate ethanol reinforcement.
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References
Amit Z, Smith BR, Gill K (1991) Serotonin uptake inhibitors: effects on motivated consummatory behaviors. J Clin Psychiatry 52(Suppl):55–60
Beardsley PM, Lemaire GA, Meisch RA (1978) Ethanol-reinforced behavior of rats with concurrent access to food and water. Psychopharmacology 59:7–11
Beardsley PM, Lemaire GA, and Meisch RA (1993) Persistence of ethanol self-administration as a function of interreinforcer interval and concentration. Drug Alcohol Depend 34:71–81
Foltin RW, Haney M, Comer SD, Fischman MW (1996) Effect of fluoxetine on food intake of humans living in a residential laboratory. Appetite 27(2):165–181
George FR (1987) Genetic and environmental factors in ethanol self-administration. Pharmacol Biochem Behav 27:379–384
Grant KA, Samson HH (1985) Oral self administration of ethanol in free feeding rats. Alcohol 2:317–321
Herling S, Woods JH (1980) Chlorpromazine effects on cocaine-reinforced responding in rhesus monkeys: reciprocal modification of rate-altering effects of the drugs. J Pharmacol Exp Ther 214:354–361
Hiltunen AJ, Jarbe TU, Hellstrom-Lindahl E, Croon LB, Jones AW (1989) Concentrations of ethanol in rebreathed air of rats: correlation with the discriminative stimulus effects of ethanol. Alcohol 6:39–43
Javors MA, Ginsburg BC, Friesenhahn G, Lamb RJ (2004) Rat breathalyzer. Alcohol Clin Exp Res 28:40A
Kelleher RT, Morse WH (1968) Determinants of the specificity of behavioral effects of drugs. Ergeb Physiol 60:1–56
Koob GF (2003) Alcoholism: allostasis and beyond. Alcohol Clin Exp Res 27:232–243
Lamb RJ, Jarbe TU (2001) Effects of fluvoxamine on ethanol-reinforced behavior in the rat. J Pharmacol Exp Ther 297:1001–1009
Lamb RJ, McMillan DE (1986) The effects of some putative antidepressant agents on the schedule-controlled behavior of the pigeon. Psychopharmacology 88:368–373
Maurel S, De Vry J, Schreiber R (1999a) Comparison of the effects of the selective serotonin-reuptake inhibitors fluoxetine, paroxetine, citalopram and fluvoxamine in alcohol-preferring cAA rats. Alcohol 17:195–201
Maurel S, De Vry J, Schreiber R (1999b) 5-HT receptor ligands differentially affect operant oral self-administration of ethanol in the rat. Eur J Pharmacol 370:217–223
McBride WJ, Murphy JM, Gatto GJ, Levy AD, Yoshimoto K, Lumeng L, Li TK (1993) CNS mechanisms of alcohol self-administration. Alcohol Alcohol Suppl 2:463–467
Murphy JM, McBride WJ, Gatto GJ, Lumeng L, Li TK (1988a) Effects of acute ethanol administration on monoamine and metabolite content in forebrain regions of ethanol-tolerant and -nontolerant alcohol-preferring (P) rats. Pharmacol Biochem Behav 29:169–174
Murphy JM, Waller MB, Gatto GJ, McBride WJ, Lumeng L, Li TK (1988b) Effects of fluoxetine on the intragastric self-administration of ethanol in the alcohol preferring P line of rats. Alcohol 5:283–286
Pohorecky LA, Brick J (1982) A new method for the determination of blood ethanol levels in rodents. Pharmacol Biochem Behav 16:693–696
Ritz MC, George FR, Meisch RA (1989) Ethanol self-administration in ALKO rats. I. Effects of selection and concentration. Alcohol 6:227–233
Roberts AJ, McArthur RA, Hull EE, Post C, Koob GF (1998) Effects of amperozide, 8-OH-DPAT, and FG 5974 on operant responding for ethanol. Psychopharmacology 137:25–32
Samson HH, Tolliver GA, Pfeffer AO, Sadeghi K, Haraguchi M (1988) Relation of ethanol self-administration to feeding and drinking in a nonrestricted access situation in rats initiated to self-administer ethanol using the sucrose-fading technique. Alcohol 5:375–385
Silvestre JS, Palacios JM, Fernandez AG, O’Neill MF (1998) Comparison of effects of a range of 5-HT receptor modulators on consumption and preference for a sweetened ethanol solution in rats. J Psychopharmacol 12:168–176
Slawecki CJ, Samson HH (1997) Changes in oral ethanol self-administration patterns resulting from ethanol concentration manipulations. Alcohol Clin Exp Res 21:1144–1149
Tomkins DM, O’Neill MF (2000) Effect of 5-HT(1B) receptor ligands on self-administration of ethanol in an operant procedure in rats. Pharmacol Biochem Behav 66:129–136
Vacca G, Serra S, Brunetti G, Carai MA, Samson HH, Gessa GL, Colombo G (2002) Operant self-administration of ethanol in Sardinian alcohol-preferring rats. Alcohol Clin Exp Res 26:1678–1685
Wilson AW, Neill JC, Costall B (1996) The 5-HT1A receptor agonist 8-OH-DPAT reduces ethanol intake and maintained behavior in female Sprague–Dawley rats. Alcohol 13:407–413
Yoshimoto K, Yoshida T, Sorimachi Y, Hirano A, Takeuchi Y, Ueda S, Yasuhara M (1998) Effects of age and ethanol on dopamine and serotonin release in the rat nucleus accumbens. Physiol Behav 64:347–351
Acknowledgements
The authors wish to thank Roslyn Martinez and Gerardo Martinez for their technical assistance during behavioral studies. The authors would also like to thank Greg Friesenhahn and Gerardo Martinez for technical assistance during breath ethanol measurements. The experiments described herein conform to all applicable laws of the United States. This work was supported by PHS grant AA012337.
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Ginsburg, B.C., Koek, W., Javors, M.A. et al. Effects of fluvoxamine on a multiple schedule of ethanol- and food-maintained behavior in two rat strains. Psychopharmacology 180, 249–257 (2005). https://doi.org/10.1007/s00213-005-2156-z
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DOI: https://doi.org/10.1007/s00213-005-2156-z