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Original Article |
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Neuropsychopharmacology (1999) 21 435-444.10.1038/sj.npp.1395348
Effects of Naltrexone and Fluoxetine on Alcohol Self-Administration and Reinstatement of Alcohol Seeking Induced by Priming Injections of Alcohol and Exposure to Stress
AD Lê1,2 Ph.D, CX Poulos1,3 Ph.D, S Harding1, J Watchus1 BSc, W Juzytsch1 and Y Shaham4 Ph.D |
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1Biobehavioral Research Department, Center for Addiction and Mental Health, Toronto, Canada
2Department of Pharmacology, University of Toronto, Toronto, Canada
3Psychology, University of Toronto, Toronto, Canada
4Behavioral Neuroscience Branch, NIDA/IRP, Baltimore, MD USA
Correspondence: Dr AD Le, Biobehavioral Research Department, CAMH, 33 Russell St. Toronto, Ontario, Canada M5S 2S1
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ABSTRACT
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We have recently shown that priming injections of alcohol and footshock stress reinstate alcohol seeking in drug-free rats. Here we tested whether naltrexone and fluoxetine, two drugs used in the treatment of alcohol dependence, would affect reinstatement of alcohol seeking induced by these events. We also determined the effects of these drugs on alcohol self-administration during the maintenance phase. Rats were trained to press a lever for a 12% w/v alcohol solution. After stable drug-taking behavior was obtained, lever pressing for alcohol was extinguished. Reinstatement of drug seeking was then determined after priming injections of alcohol (0.24-0.96 g/kg) or exposure to intermittent footshock (5 and 15 min). Rats were pretreated with naltrexone (0.2-0.4 mg/kg) or fluoxetine (2.5-5 mg/kg) during maintenance or during tests for reinstatement. Both naltrexone and fluoxetine decreased lever presses for alcohol during the maintenance phase. Naltrexone blocked alcohol-induced, but not stress-induced reinstatement. In contrast, fluoxetine blocked stress-induced reinstatement, while its effect on alcohol-induced reinstatement was less consistent. The implications of these data to the understanding of relapse to alcohol are discussed.
Keywords: Alcohol; Drug self-administration; Fluoxetine; Naltrexone; Opioid receptors; Relapse; Reinstatement; Serotonin; Stress |
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