S50 Behavioural pharmacology All results are presented as group means (±SEM). Differences in behavioral scores and in the levels of genes expression between EE and SE were assessed by one or two-way ANOVA followed, when appropriate, by Student- Newmann-Keuls post-hoc test. A probability value of p < 0.05 was considered significant. Results: The rewarding effects of Heroin (1 and 2 mg/kg) are blunted in EE mice compared to SE mice (P < 0.05). Both EE and SE mice develop behavioral sensitization to heroin with no significant difference in the locomotor activity in response to repeated injections of heroin (1 mg/kg s.c). Furthermore, we found no difference in response to heroin challenge (0.66 mg/kg s.c) between SE mice and EE mice one month after the last injection of heroin. Finally, heroin-induced increases in early immediate genes (c-fos and Zif-268) did not differ between EE and SE mice. Conclusions: These results demonstrate that enriched environments protect against the rewarding effects of heroin but do not affect the activating effects of repeated injections of heroin. In addition, the reactivity to heroin of striatal neurons is not altered by enriched environment. Thus, a dichotomy exists between the rewarding effects of heroin and its ability to increase locomotor activity and expression of immediate early genes in the striatum. However, since rewarding effects rather than stimulant effects appear to be central for the development of opiate addiction, the present results suggest that environmental enrichment during early ages provide protection against heroin dependence. Reference(s) [1] Bezard E, Dovero S, Belin D, Duconger S, Jackson- Lewis V, Przedborski S, Piazza PV, Gross CE, Jaber M, 2003, Enriched environment confers resis- tance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and cocaine: involvement of dopamine transporter and trophic factors. J Neurosci 23, 10999–11007. [2] Solinas M, Thiriet N, El Rawas R, Lardeux V, Jaber M, 2007, Environmental enrichment during early stages of life reduces the behavioral, neurochemical and molecular effects of cocaine. Presented at Motivational Neural Network (MNN) Meeting, Porquerolles, May 2007. P.2.17 Estradiol decreases ventral tegmental area self-stimulation threshold and increases cocaine rewarding properties in rats T. Galankin 1 ° , I.V. Belozertseva 1 , E.V. Shekunova 1 , E.E. Zvartau 1 . 1 Pavlov Medical University, Institute of Pharmacology, St. Petersburg, Russia Purpose of the study: Women initiate cocaine use at a younger age and have more complications related to cocaine use than men. It has been proposed that estrogens play an important role in these gender differences. For example, subjective effects from smoked cocaine in women depend on the level of estradiol in blood serum [1]. Addictive potential of psychoactive drugs can be measured in rats via rewarding intracranial self-stimulation (ICSS) procedure [2]. Rate-independent method of ICSS described by Kornetsky [2] allows to assess “pure” rewarding effect of cocaine without influence of nonspecific motor reactions. Rewarding effect of estradiol in this procedure has never been shown. The goal of this study was to estimate effects of estradiol and a combination of estradiol and cocaine on the ICSS in ovariectomized female rats. Methods used: ICSS procedure with slight changes was adopted from Kornetsky. The subjects were individually housed female Wistar rats, which were ovariectimized and stereotaxically implanted with bipolar stainless steel electrodes, aimed at the ventral tegmental area. The animals were tested daily in an experimental chamber. Biphasic square wave stimuli were delivered by a constant current stimulator. The procedure involved the use of discrete trials systematically presented over a range of stimulus intensities. A trial began with the delivery of a noncontingent stimulus. A response (nose-poke) resulted in a contingent stimulus, identical in all parameters to the noncontingent stimulus. Failure to respond had no scheduled consequences. Responses during the intertrial interval (error responses) resulted in a 15 sec delay before the start of the next trial. Depending on the rats’ responding or not responding to the noncontingent stimulus current intensities were varied in alternating descending and ascending series. The arithmetic mean of minimal current intensities that were sufficient to elicit responding in these series was determined as the threshold for ICSS. The study consisted of 2 separate experiments. In the first experiment effect of beta-estradiol benzoate (5 mkg/animal/day dissolved in sesame oil, SC, 2 days of injection) or its vehicle on the threshold for ICSS was established. The second experiment