Maternal separation stress in male mice: long-term increases in alcohol intake

Abstract

In rodents, prolonged maternal separation has been used as a model of developmentally early environmental stress to influence adult drug intake. The aim of the present study was to evaluate the long-term effects of prolonged maternal separation on alcohol consumption using two different self-administration procedures in mice: operant alcohol self-administration vs. three-bottle choice. From postnatal day (PND) 1 to 14, pups were separated from the dam (maternal separation, MS) daily for 180 min or were left undisturbed, only handled during cage cleaning (animal facility rearing, AFR). On PND 60, they were assigned to one of two experimental manipulations: either a three-bottle choice or operant oral alcohol self-administration. In the three-bottle choice procedure, mice were given access to 6% or 10% alcohol or 0.05% saccharin solution for 2 h/day for 10 days. In the second experiment, mice were reinforced for nose poking by delivery of oral alcohol (6% or 10% in saccharin) or 0.05% saccharin solutions during daily 30-min sessions. Following the acquisition phase, "break points" were determined. Later, mice were allowed 1 h access to the reinforcing solution with no dosage limitation. In the three-bottle choice procedure, MS mice showed higher alcohol intake than AFR at the 10% alcohol concentration. In the operant alcohol self-administration, MS mice achieved higher alcohol intake than AFR at the concentrations 6% and 10% during the 1-h session. The results demonstrate the long-term consequences of MS on alcohol intake in male mice, suggesting early life stress as a risk factor for alcohol consumption and abuse.