Post-weaning Environmental Enrichment, But Not Chronic Maternal Isolation, Enhanced Ethanol Intake during Periadolescence and Early Adulthood

Abstract

This study analyzed ethanol intake in male and female Wistar rats exposed to maternal separation (MS) during infancy (postnatal days 1–21, PD1–21) and environmental enrichment (EE) during adolescence (PD 21–42). Previous work revealed that MS enhances ethanol consumption during adulthood. It is still unknown if a similar effect is found during adolescence. Several studies, in turn, have revealed that EE reverses stress experiences, and reduces ethanol consumption and reinforcement; although others reported greater ethanol intake after EE. The interactive effects between these treatments upon ethanol’s effects and intake have yet to be explored. We assessed chronic ethanol intake and preference (12 two-bottle daily sessions, spread across 30 days, 1st session on PD46) in rats exposed to MS and EE. The main finding was that male – but not female – rats that had been exposed to EE consumed more ethanol than controls given standard housing, an effect that was not affected by MS. Subsequent experiments assessed several factors associated with heightened ethanol consumption in males exposed to MS and EE; namely taste aversive conditioning and hypnotic-sedative consequences of ethanol. We also measured anxiety response in the light-dark box and in the elevated plus maze tests; and exploratory patterns of novel stimuli and behaviors indicative of risk assessment and risk-taking, via a modified version of the concentric square field (CSF) test. Aversive conditioning, hypnosis and sleep time were similar in males exposed or not to EE. EE males, however, exhibited heightened exploration of novel stimuli and greater risk taking behaviors in the CSF test. It is likely that the promoting effect of EE upon ethanol intake was due to these effects upon exploratory and risk-taking behaviors.

Treatment with 1‐benzylpiperazine (BZP) during adolescence of male and female hooded rats exposed to environmental enrichment: Subsequent behavioral outcomes

“…From the main results of this study, it can be concluded that, while treatment with BZP during adolescence led to higher anxiety at older ages, this was more typical of rats housed in enriched rather than in standard cages thereby suggesting that enrichment had enhanced the anxiogenic action of the drug. So contrary to expectations, enrichment did not appear to have provided protection from the development of BZP‐related higher anxiety reported previously (Aitchison and Hughes, 2006) similar to reports of increased voluntary ethanol consumption in rats (Berardo et al, 2016; Rockman et al, 1989). The possibility that enrichment may in some situations be detrimental rather than beneficial is not consistent with most of the literature and, as suggested by van Praag et al (2000), requires further investigation.…”

“…It is also inconsistent with reductions in the reinforcing value and thus addiction potential of other drugs such as heroin (El Rawas et al, 2009), cocaine (Solinas et al, 2008) and ethanol (Holgate et al, 2017). However, there are also examples of enrichment having the opposite effect such as increasing ethanol's reinforcing value (Berardo et al, 2016) thereby detracting from any perceived beneficial quality of the manipulation. It is accordingly possible that, in the present study, enrichment was similarly detrimental with respect to the action of BZP during adolescence.…”

“…It is accordingly possible that, in the present study, enrichment was similarly detrimental with respect to the action of BZP during adolescence. Because potentially detrimental effects of ethanol are more evident following treatment during adolescence (Berardo et al, 2016), such a possibility for BZP is clearly worthy of further investigation. Although the nature of the present study precluded determination of any neurochemical basis for possible enhancement of the anxiogenic effects of adolescent BZP, it might be interesting in future to consider similarities in some central effects of the two manipulations such as, for example, increased dopaminergic and serotonergic activity with both BZP treatment (Baumann et al, 2004; Monteiro et al, 2013) and exposure to enrichment (Brenes et al, 2008; Darna et al, 2015).…”

“…However, enrichment can influence drug effects in different ways. For example, it has been shown to either increase voluntary consumption and the reinforcing value of ethanol in rats (Berardo et al, 2016; Rockman et al, 1989) and mice (Rae et al, 2018), or have the opposite effect in both species respectively (Deehan et al, 2007; Holgate et al, 2017). It was therefore conceivable that BZP experienced repeatedly during adolescence in conjunction with enrichment might also differ in its subsequent effects on anxiety‐related behavior from those following acute administration of other drugs during adulthood.…”

Amphetamine, but not methylphenidate, increases ethanol intake in adolescent male, but not in female, rats

“…These traits have been long considered phenotypes associated with propensity for ethanol intake. We have recently observed, for instance, that rats selectively bred for high ethanol intake during adolescence significantly avoided the white, potentially dangerous, chamber of a light-dark box (Fernandez et al, 2017); and in other study, we found that male rats reared under environmental enrichment exhibited both enhanced ethanol intake and behaviors indicative of greater risk-taking, when compared to counterparts reared under standard conditions (Berardo, Fabio, & Pautassi, 2016). In the present study, however, the patterns of exploration of the light-dark box were similar in AMPH, MPH, and vehicle-treated rats.…”