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

Abstract

Rationale In rodents, prolonged maternal separation has been used as a model of developmentally early environmental stress to influence adult drug intake. Objectives 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. Materials and methods 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. Results 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. Conclusions 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.

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

“…In general, studies reveal a Ushaped time-dependent effect in which MS60-360 and control (NH or AFR) groups show greater alcohol intake relative to MS15 in both rats (Hilakivi-Clarke et al, 1991;Ploj et al, 2003a;Roman et al, 2003;Jaworski et al, 2005) and mice (Cruz et al, 2008). However, Huot et al (2001) failed to observe a difference between male MS15 and AFR controls, although MS180 males did exhibit enhanced alcohol intake relative to AFR controls.…”

Maternal separation and proclivity for ethanol intake: A potential role of the endocannabinoid system in rats

“…Individual vulnerability to develop alcohol dependence is determined by the combination of genetic and environmental factors (Enoch and Goldman, 2001;Goldman et al, 2005;Enoch, 2012). Among the environmental challenges that may contribute to the development of a preference for alcohol ingestion is the maternal separation (MS) (Cruz et al, 2008;Becker et al, 2011). It has been considered one of the most powerful stressors for infants (Levine, 2001(Levine, , 2005, producing long-lasting neural changes that increase vulnerability to alcohol and dependence to other drugs in adulthood (Levine, 2001;Gilmer and McKinney, 2003;Moffett et al, 2007).…”

How Do We ‘Learn' Addiction? Risk Factors and Mechanisms Getting Addicted to Alcohol

“…In animal studies, early maternal separation was followed by higher alcohol consumption in mice and rats [24,25]. Several animal studies suggest that the heightened vulnerability to substance abuse results from alterations of the hypothalamic-pituitary-adrenal axis due to stressful events in the first weeks of life or even prenatally [25,26,27], enhancing sensitivity to stressors.…”

“…Several animal studies suggest that the heightened vulnerability to substance abuse results from alterations of the hypothalamic-pituitary-adrenal axis due to stressful events in the first weeks of life or even prenatally [25,26,27], enhancing sensitivity to stressors. Other parts of the hormonal systems controlling responses to stress outside the hypothalamus seem to be implicated in the regulation of alcohol intake due to stressful events as well [28,29].…”