Manipulation of operant responding for an ethanol-paired conditioned stimulus in the rat by pharmacological alteration of the serotonergic system

It is becoming increasingly clear that environmental stimuli play a critica l role in the maintenance of drug taking behaviour. This has led to investi gations into the neural mechanisms by which environmental stimuli can come to control behaviour using paradigms such as conditioned reinforcement. The majority of this work has involved the use of food-paired conditioned stim ulus rodent paradigms. Relatively few studies have attempted to investigate the neuropharmacology of behaviour maintained by presentation of a stimulu s paired with ethanol drinking. Several lines of research support an import ant role for brain serotonin (5-HT) neurotransmitter systems in the control of alcohol drinking behaviour. The aim of the present study was, initially , to establish a procedure in which rats respond for an ethanol-paired cond itioned stimulus, and second, to study the effects of a range of serotonerg ic compounds previously shown to be effective in reducing oral ethanol self -administration, on responding for this conditioned stimulus. Results showe d that the 5-HT releaser d-fenfluramine, the selective serotonin reuptake i nhibitor fluoxetine, the 5HT(1A) receptor agonist 8-hydroxy-2[di-n-propylam ino]tetralin, the partial 5-HT1A receptor agonist buspirone, and the 5-HT1B /5-HT2C receptor agonist 1-(3-trifluoromethylphenyl)piperazine, but not the 5-HT2A/5-HT2C receptor against 1-(2,5-dimethoxy-4-iodophenylaminopropane)- 2 selectively reduced responding on a lever leading to presentation of an e thanol paired conditioned stimulus. In addition the non-specific D-1/D-2 do pamine receptor antagonist haloperidol was active in this paradigm. Results are consistent with involvement of the dopaminergic and 5-HT systems, in p articular activation of 5-HT1A and 5-HT1B receptor subtypes, in mediation o f the conditioned or secondary reinforcing properties of ethanol.