Introduction The locomotor stimulant effects of the psychostim- ulants amphetamine or cocaine as well as those of other addictive agents such as opiates, nicotine or ethanol become progressively greater with chronic intermittent exposure. This phenomenon is known as sensitization. Cross-sensitization between psychos- timulants and opiates has been reported suggesting that a common neural system may be affected by many different drugs (see Ref. 1 for review). In fact, these drugs share the ability to activate mesotelen- cephalic dopamine (DA) systems, especially their projections to the ventral striatum (see Refs 1, 2 for reviews). Recent experiments, using either self-administra- tion procedures or the conditioned place preference paradigm (CPP), in which the place where a drug is experienced becomes preferred by the animal in a subsequent choice test, 3,4 indicate that prior expo- sure to some addictive drugs, such as amphetamine, cocaine or morphine, also produces sensitization to their rewarding effects. 2 This sensitization to the motivational properties of drugs may be espe- cially relevant in drug-seeking behavior and rein- statement of drug-taking by addicts after a period of abstinence. Some data suggest that cross-sensitization to the reinforcing effects develops as well. 2 In particular, for cocaine, pre-exposure to cocaine but also to amphetamine or nicotine facilitates the later acquisition of cocaine self-administration. 5,6 Using the CPP paradigm, sensitization is observed after repeated administration of amphetamine, cocaine or morphine and animals pretreated with amphetamine or morphine show an enhanced conditioned place preference for cocaine. 7–9 Ethanol is a rather weak reinforcer in rats. 10 For instance, using the CCP paradigm, the positive rein- forcing effects of ethanol have been demonstrated only in rats with a history of ethanol exposure. 11–14 Nonetheless, stimulation of DA release in the nucleus accumbens has been demonstrated after systemic administration of low doses of ethanol as well as during voluntary oral self-administration. Both the locomotor and reinforcing actions of ethanol have been linked to this increase in DA transmission (see Refs 15, 16 for references). Moreover, a decrease in basal dopamine release in the nucleus accumbens after ethanol withdrawal further implicates DA transmis- sion in alcohol dependence. 17 Repeated ethanol treat- ment results in a long-term increase in the electrically evoked release of [ 3 H]DA from slices of the nucleus Neuropharmacology 1111 2 3 4 5 6 7 8 9 10111 1 2 3 4 5 6 7 8 9 20111 1 2 3 4 5 6 7 8 9 30111 1 2 3 4 5 6 7 8 9 40111 1 2 3 4 5 6 7 8 9 50111 1 2 3 4 5 6111p 0959-4965 © 1998 Lippincott Williams &Wilkins Vol 9No 1 224 August 1998 2887 THE conditioned place preference (CPP) induced by cocaine 2. 5mg/kg was measured in rats pre-exposed to ethanol (14 days with only 10% v/v ethanol followed by a free choice between ethanol solution and water for 14 days). Rats were divided according to their alcohol intake during the free choice period into low-drinking ( <3 g/kg per day), intermediate-drinking and high- drinking ( >4 g/kg per day) rats. Cocaine-induced CPP was not modified in high-drinking rats relative to controls. Low-drinking rats had a lower CPP than high- drinking rats and controls. We conclude that pre- exposure to alcohol did not sensitize to the cocaine rewarding effects, and that alcohol low-drinking rats showed the lowest preference for cocaine . NeuroReport 9: 2887–2891 © 1998 Lippincott Williams & Wilkins. Key words: Cocaine; Conditioned place preference; Ethanol; Free choice; Individual differences; Rat Pre-exposure to alcohol does not sensitize to the rewarding effects of cocaine Gwenaëlle Le Pen, Dominique Duterte-Boucher, CA Martine Daoust 1 and Jean Costentin Unité de Neuropsychopharmacologie Expérimentale, UPRESA 6036 du CNRS, Institut Fédératif de Recherche Multidisciplinaire sur les Peptides, Faculté de Médecine et de Pharmacie de Rouen, 76803 Saint Etienne du Rouvray; 1 Laboratoire de Physiologie, Université de Picardie Jules Verne, 80025 Amiens, France CA Corresponding Author Website publication 12 August 1998 NeuroReport 9, 2887–2891 (1998)