The gut-brain peptide ghrelin is recognized as an important CNS target for the control of food intake. The aim is to investigate whether acute alcohol intake changes the levels of plasma ghrelin in different aged mice, and how alcohol influences lateral hypothalamus (LH) ghrelin levels and the expression of growth hormone secretagogue receptor 1A (GHSR-1A) mRNA in habitual alcohol drinking model. Exp.1: Effects of EtOH (2 g/kg,i.p.) administration at 1, 3 and 10 months old on the levels of plasma ghrelin in alcohol-naïve C57BL/6J mice and one- and 20-day alcohol vapor-exposed C57BL/6J mice, as non-habitual alcohol drinking model (NHAD) and habitual alcohol drinking model (HAD), respectively. Plasma ghrelin levels in the naïve mice decreased with the EtOH administration. Plasma ghrelin levels of the HAD increased at 1 and 2 hr after the administration of EtOH, compared with the NHAD. Exp.2: Effects of acute EtOH (2 g/kg, i.p.) on in vivo LH ghrelin release in the NHAD and HAD, using in vivo push-pull brain peptide microdialysis. LH ghrelin release increased in both NHAD and HAD after the administration of EtOH. Exp.3: Expression of LH GHSR-1A mRNA in the NHAD and HAD. The expression of LH GHSR-1A mRNA increased in the HAD significantly. Exp. 4: Effects of EtOH (2 g/kg, i.p.) on the releases of LH DA and 5-HT in the NHAD and HAD. The administration of EtOH (2 g/kg. i.p.) increased the LH DA, not 5-HT, release in the NHAD. On the other hand, EtOH administration increased both LH DA and 5-HT releases in the HAD. It was suggested that habitual alcohol drinking behavior involved with the neural cooperation of the G protein-coupled receptors, especially ghrelin and serotonin receptors in the LH.