1997, FEBS Lett 412, 35–38; Walker et al., 1999, Eur J Pharmacol 383, 115–119). A unique 6-MAM/M6G subreceptor or splice variant responsible for their analgesic activity has been proposed. Whether this also accounts for the stimulating properties of these opioids, has however not been investigated. Therefore, we explored the antagonizing effects of 3- MeONtx and naltrexone (NTX) on the acute stimulating effects of heroin, 6-MAM and morphine in mice, and their pharmacokinetic profiles. 3-MeONtx (0.5 or 2.5 mg/kg) or NTX (0.05 or 0.5 mg/kg) was given intra- peritoneally 15 min before heroin (5–50 mmol/kg), 6-MAM (5–50 mmol/kg) or morphine (10–80 mol/kg) was administered subcutaneously in male C57BL/6 J mice. The locomotor activity was then recorded for 1 h. Separate groups of mice were sacrificed at different time points following antagonist administration, and their brains were analyzed for 3-MeONtx or NTX using LC-MS/MS. Pretreatment with 3-MeONtx blocked the increase in locomotor activity induced by heroin, 6-MAM, and morphine. Administra- tion of 3-MeONtx or NTX gave similar pharmacokinetic profiles in mouse brain, and besides potency disparities, no clear difference in antagonizing effect was observed between 3-MeONx and NTX. 3-MeONtx is no more selective in antagonizing the acute stimulating effects of heroin and 6- MAM than that of morphine in mice. This indicates that the stimulating effects of these opioids are mediated by a population of similar m-OR, and further that their analgesic- and stimulating effects are mediated by different m-OR splice variants or mechanisms in mice. E.14 - EFFECTS OF CURCUMIN ON BRAIN STIMULATION REWARD AND THE REWARD- FACILITATING EFFECT OF MORPHINE Vicky Katsidoni a , Marilena Fotiadou b , Marina Sagnou c and George Panagis a a University of Crete, Department of Psychology, Laboratory of Behavioral Neuroscience, 74100 Rethymno, Crete, b City Unity College, Department of Psychology, 15-17Thiseos str, Syntagma,Athens, T.K. 10562 and c National Centre for Scientific Research Demokritos, Institute of Biology, 15310 Ag. Paraskevi, Attiki, Athens, Greece Curcumin is a multimodal polyphenol natural product isolated from the plant Curcuma longa. Recent animal studies reported that curcumin has several central actions, among which are an antidepressant and a neuroprotective effect. In the present study we utilized the intracranial self-stimulation (ICSS) paradigm to examine the effects of the commercially available curcuminoid mixtrure, pharmaceutically used as food supplement, on brain reward and on the reward-facilitating effect of morphine. To the best of our knowledge, this is the first study on the effects of curcumin on brain stimulation reward and the reward- facilitating effect of opioids. Male Sprague-Dawley rats were implanted with a monopolar electrode into the medial forebrain bundle (MFB) and were trained to respond for electrical stimulation using a rate-frequency paradigm. In the first experiment, rats were injected with curcumin (5, 10 and 20 mg/kg, i.p.). The highest doses of curcumin tested significantly increased the threshold frequency required for MFB ICSS. In a second experiment, we examined whether curcumin (5 mg/kg, i.p.) could counteract the reward-facilitating effect of morphine (10 mg/kg, s.c.). Curcumin inhibited the reward-facilitating effect of morphine, at a dose that did not by itself affect brain reward function. The present results indicate that curcumin does not exhibit reinforcing properties in the ICSS paradigm over a range of doses tested, but rather has an inhibitory influence on reward mechanisms at high doses and even reduces the reward-facilitating effect of morphine. The present data indicate that curcumin interferes with brain reward mechanisms responsible for the expression of the acute reinforcing properties of opioids and provide evidence that curcumin may be used as a food supplement in attenuating the rewarding effects of opioids. E.15 - GHRELIN RECEPTOR ANTAGONISM ATTENUATES MORPHINE-INDUCED ACCUMBAL DOPAMINE RELEASE AND BEHAVIORAL STIMULATION IN RATS Sustkova-Fiserova Magdalena a , Jerabek Pavel a , Havlickova Tereza a , Kacer Petr b and Krsiak Miloslav a a Department of Pharmacology, 3rd Faculty of Medicine, Charles University, Ruska 87, Prague 10, 100 34 and b Laboratory of medicinal diagnostics, Department of organic technology ICT, Technicka 5, Prague 6, 166 28, Czech Republic Aims of the study: An orexigenic appetite regulating peptide ghrelin activates binding sites in the ventral tegmental area, a structure linked with reward, thus probably participating in reward-seeking behavior. An increasing number of studies during the last years indicates ghrelin ´s participation in alcohol abuse, several also focused on cocaine and nicotine abuse. However the role of ghrelin in opioid dependence has been only rarely studied yet. Thus, we wanted to determine, whether the central ghrelin signaling system participates also in the reward processes of opiods, namely morphine. Methods: We used ‘‘in vivo’’ microdialysis to determine the changes in concentrations of dopamine and its metabolites in the nucleus accumbens shell (NACSh) in rats following morphine (MO, 5, 10 mg/kg s.c.) injection with or without ghrelin antagonist pretreatment (JMV2959, 6 mg/kg i.p. 20 min before MO). The induced behavioral changes were simultaneously monitored. Results: For both doses morphine-induced behavioral stimulation was significantly reduced by the JMV2959 pretreatment, especially with regards to stereotypes. JMV2959 also significantly reduced the morphine-induced enhancement of accumbal dopamine release. The morphine-induced enhanced dopamine metabolism was also influenced by JMV2959 pretreatment (after pretreatment owith the lower MO dose, accumbal 3-MT level was decreased, while DOPAC and HVA levels were increased after pre-treatment with the higher MO dose). Conclusion: GHS-R1A appears to be required for opioid-induced reward. Our data confirm that the central ghrelin signaling system might constitute a novel potential target for the treatment of drug dependence. This work was supported by projects IGA MHCR NT/ 13687–3/2012, GAUK 54313 and PRVOUK P34. E.16 - SELECTIVE MODULATION OF THE MOTOR SUPPRESSANT EFFECTS OF NICOTINE BY THE GABA- A RECEPTOR ANTAGONIST, BICUCULLINE Rajeev I. Desai a and Philip Terry b a Preclinical Pharmacology Laboratory, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA and b Department of Psychology, Kingston University London, Kingston-upon-Thames, Surrey KT1 2EE, UK The acute administration of nicotine reliably produces dose- and time-dependent decreases in motor activity in laboratory rodents; however, the neurochemical mechanisms that underlie this effect have not yet been identified. The present series of experiments was conducted to evaluate the contributions of nicotinic, dopaminergic, and GABAergic receptor mechanisms in the acute motor suppressant effects of nicotine. Using a time-sampling observational procedure, the effects of nicotine alone and in combination with a nicotinic (mecamylamine), dopaminergic (flupenthixol), GABA-A (bicuculline), and GABA-B (saclofen) receptor antagonist were determined over a 40 min observation period in male CD1 mice (n = 8/treatment group). Nicotine (0.1–1.0 mg/kg) alone produced a dose-related and time- dependent decline in motor activity (i.e., immobility frequency EBPS Workshop Abstracts e45 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.