Alcoholism is one of the most costly diseases afflicting population worldwide.The nucleus accumbens is a basal forebrain structure situated deep in the grey matter1. It is one of the major component of the reward system2.The present study was designed to elucidate role of Orexin B in ethanol consumption and glutamate levels in the nucleus accumbens.All procedures were performed as per the guidelines established by the Institutional Animal Ethics Committee (IIAEC/KMC/57/2009-2010).Eighteen male rats were divided into 3 groups i.e. Control, Treated 1(3nm/µl) and Treated 2(30nm/µl)( (n=6).The rats were anaesthetized with a cocktail of ketamine (60 mg/kg BW) and xylazine (10 mg/kg BW) injected intraperitoneal route.The nucleus accumbens lesion was performed according to the stereotaxic coordinates as prescribed in the Paxinos and Watson3. Post infusion, in overnight fasted rats, alcohol and food intake was measured meticulously after 1 hour, 2 hours, 4hours, 6 hours, 12 hours and 24 hours. Further glutamate levels in the specific brain nuclei were estimated. The animal was decapitated and the brain tissue homogenate was used for the analysis. Glutamate was quantified using a commercially available ENZYTMCHROM GLUTAMATE ASSAY KIT (Bioassay systems, USA; catalogue number: EGLT-100) according to the manufacturer’s protocol.Data were expressed as mean±SEM (ANOVA; Student-Newman Keuls test,).P<0.05 were considered as statistically significant. The high dose (HD) of Orexin B increased ethanol consumption (10%) significantly at the end of 1,2,4,12,24 hrs. In low doses(LD) of Orexin B (3nm/µl) there was significant increase in alcoholintake1,4,12and24hrs.[C(3.1±0.48,2.9±0.18,3.7±0.34,4.54±1.19,16.62±1.20)LD(6.8±0.70,3.78±0.38,4.8±0.35,7.16±1.36,20.85±1.53)HD(10.1±0.6,5.28±0.35,6.64±0.42,8.76±0.91,26±0.85)].Food intake was also increased significantly at the end of 1 and 4 hrs(p<0.001)[C( 2.3±0.36,0.69±0.20,0.34±0.05,6.9±0.71,10.26±1.05)LD(5.39±0.500.83±0,27,1.31±0.08,5.47±1.01,13.01±1.44)HD(6.2±0.4,0.94±0.14,2.18±0.09 ,8.62±0.60,17.96±0.99).Glutamate levels of nucleus accumbens were significantly decreased with the infusion of Orexin B into the same nucleus(p<0.0001)aswellasBLA(p<0.01).[NAcc(72.5±0.45,55.49±0.48);BLA(57.44±0.30,63.2±1.21).This result suggests that infusion of Orexin B into NAcc bilaterally, led to increase in alcohol and food and decrease in glutamate may be due short-term consumption of ethanol. Key words; Orexin Nucleus accumbens, ethanol, lesion.