Elevated alcohol consumption in mice lacking functional natriruetic peptide-A receptor

Background: Recent results suggest that the endocrine system can influence alcohol intake and modulate ethanol drinking behavior. In mice and humans a correlation has been found between ANP plasma concentration and craving, anxiety as well as the severity of the withdrawal symptoms. To further elucidate the involvement of the natriuretic peptide system in neurobehavioral effects of alcohol, we examined ethanol consumption and relapse behavior in mice lacking a functional natriuretic peptide-A (NPR-A) receptor. Methods: NPR-A heterozygote, -knockout and wild-type mice were given a free choice between water and increasing concentrations of ethanol (2–16%). Once a stable baseline of 16% ethanol consumption was established, access to ethanol was withdrawn for 2 weeks and then reinstated in order to measure the alcohol deprivation effect (ADE). A forced swim stress was performed thereafter on 3 consecutive days. Results: Data analysis revealed a higher ethanol preference and increased free-choice ethanol intake in NPR-A-transgenic mice compared with their wildtype littermates. Throughout the experiments the ethanol intake was highest in heterozygote animals. In contrast, stress-induced drinking (three consecutive days of forced swim stress) led to an immediate increase in ethanol consumption in especially the homozygote subgroup that persisted for 6 days. Deprivation from alcohol resulted in a classical ADE in all genotypes with increased ethanol intake following the deprivati