Is the rodent maternal separation model a valid and effective model for studies on the early-life impact on ethanol consumption?

Abstract

RationaleEarly-life events can cause long-term neurobiological and behavioural changes with a resultant effect upon reward and addiction processes that enhance risk to develop alcohol use disorders. Maternal separation (MS) is used to study the mediating mechanisms of early-life influences in rodents. In MS studies, the pups are exposed to maternal absence during the first postnatal weeks. The outcome of MS experiments exhibits considerable variation and questions have been raised about the validity of MS models.ObjectivesThis short review aims to provide information about experimental conditions that are important to consider when assessing the impact of early-life environment on voluntary ethanol consumption.ResultsThe results from currently used MS protocols are not uniform. However, studies consistently show that longer separations of intact litters predispose for higher ethanol consumption and/or preference in adult male rats as compared to shorter periods of MS. Studies using individual pup MS paradigms, other controls, low ethanol concentrations, adult females or examining adolescent consumption reported no differences or inconsistent results.ConclusionsThere is no “a rodent MS model”, there are several models and they generate different results. The compiled literature shows that MS is a model of choice for analysis of early-life effects on voluntary ethanol consumption but there are examples of MS paradigms that are not suitable. These studies emphasize the importance to carefully designed MS experiments to supply the optimal conditions to definitely test the research hypothesis and to be particulate in the interpretation of the outcome.

Subgroup-dependent effects of voluntary alcohol intake on behavioral profiles in outbred Wistar rats

“…Using the modified intermittent access paradigm with three consecutive days of access to 20% alcohol for seven weeks, the median alcohol intake during the last week of access in all alcohol-drinking animals was 3.2 g/kg (1.8-5.8 g/kg) and the preference was 36.4% (16.0-46.2%). This is in agreement with previous studies using intermittent access paradigms in which alcohol consumption up to 6 g/kg has been described [22,[29][30][31][32] and higher compared to studies in which Wistar rats were given continuous alcohol access [20,31,33]. Moreover, compared to our recent study [16] in which the animals had intermittent access to 20% alcohol on Mondays, Wednesdays and Fridays the modified model used herein resulted in a higher alcohol intake and a higher preference as well as an increased intake and preference over time.…”

Enhancing glutamatergic transmission during adolescence reverses early-life stress-induced deficits in the rewarding effects of cocaine in rats

“…It should be noted that this involved extensive handling and repeated IP injections over a three week period during adolescence. It has been well documented that various manipulations to rodents during the early-life period can have profound effects on hedonic behaviour in adulthood (Flagel et al, 2003;Kosten et al, 2000Kosten et al, , 2005Kosten et al, , 2006Lynch et al, 2005;Martini and Valverde, 2012;Matthews et al, 1999;Moffett et al, 2006Moffett et al, , 2007Nylander and Roman, 2013;Silveira et al, 2010;Yajie et al, 2005), as such, we conducted a separate experiment where maternally-separated animals were injected with vehicle alone, while another group of maternallyseparated animals received no injections during the adolescent period. We found the maternal-separation induced reduction in cocaine-taking remained intact independent of whether the animals had received adolescent handling and injections or had not (presented as area under the curve for reasons of succinctness).…”

An overview of maternal separation effects on behavioural outcomes in mice: Evidence from a four-stage methodological systematic review

“…Because the HPA axis is frequently dysregulated in physical and psychiatric illnesses (Andersen and Teicher, 2009;Baumeister et al, 2014;Teicher and Samson, 2013), and its altered function has been reported as a vulnerability condition for the development of psychopathology phenotypes, such as depressive and anxiety phenotypes (Andersen, 2015;Cirulli et al, 2003;Franklin et al, 2012;Pryce and Feldon, 2003), Consequently, there is a special interest in preclinical studies in developing and validating naturalistic models that are able to approximate human ELS conditions (Molet et al, 2014;Nylander and Roman, 2013;Schmidt et al, 2011;Vetulani, 2013). However, for animals the repertoire of early life conditions is more restricted, making comparisons with humans difficult (Heim and Nemeroff, 2002;Teicher et al, 2006).…”

“…Although maternal separation is the ELS model most often used to replicate early adversities, other paradigms with briefer or longer periods of separation have also been investigated (for an overview of all postnatal separation models, see Gutman and Nemeroff, 2002;Heim and Nemeroff, 2002;Pryce and Feldon, 2003;Veenema, 2009). 5 The major effect of the significant increase in postnatal separation models in the literature is evident in the heterogeneity of definitions and methodological procedures adopted by such studies (Anisman et al, 1998;Molet et al, 2014;Nishi et al, 2014;Nylander and Roman, 2013;Schmidt et al, 2011;Vetulani, 2013). Consensus on defining the steps to be followed by postnatal separation models is lacking.…”

“…Numerous postnatal manipulation models were developed with different methodologies, causing some difficulty in the interpretation of ELS developmental effects (Nylander and Roman, 2013;Vetulani, 2013). The classical model, which entails early separation of the pups from dams for a long period during the first two or three weeks, is known as the maternal separation paradigm; it has been studied increasingly in recent decades.…”