Ethanol Sensitization during Adolescence or Adulthood Induces Different Patterns of Ethanol Consumption without Affecting Ethanol Metabolism

Abstract

In previous study, we demonstrated that ethanol preexposure may increase ethanol consumption in both adolescent and adult mice, in a two-bottle choice model. We now questioned if ethanol exposure during adolescence results in changes of consumption pattern using a three-bottle choice procedure, considering drinking-in-the-dark and alcohol deprivation effect as strategies for ethanol consumption escalation. We also analyzed aldehyde dehydrogenase (ALDH) activity as a measurement of ethanol metabolism. Adolescent and adult Swiss mice were treated with saline (SAL) or 2.0 g/kg ethanol (EtOH) during 15 days (groups: Adolescent-SAL, Adolescent-EtOH, Adult-SAL and Adult-EtOH). Five days after the last injection, mice were exposed to the three-bottle choice protocol using sucrose fading procedure (4% + sucrose vs. 8%–15% ethanol + sucrose vs. water + sucrose) for 2 h during the dark phase. Sucrose was faded out from 8% to 0%. The protocol was composed of a 6-week acquisition period, followed by four withdrawals and reexposures. Both adolescent and adult mice exhibited ethanol behavioral sensitization, although the magnitude of sensitization in adolescents was lower than in adults. Adolescent-EtOH displayed an escalation of 4% ethanol consumption during acquisition that was not observed in Adult-EtOH. Moreover, Adult-EtOH consumed less 4% ethanol throughout all the experiment and less 15% ethanol in the last reexposure period than Adolescent-EtOH. ALDH activity varied with age, in which older mice showed higher ALDH than younger ones. Ethanol pretreatment or the pattern of consumption did not have influence on ALDH activity. Our data suggest that ethanol pretreatment during adolescence but not adulthood may influence the pattern of ethanol consumption toward an escalation in ethanol consumption at low dose, without exerting an impact on ALDH activity.

Effects of Ethanol Exposure During Adolescence or Adulthood on Locomotor Sensitization and Dopamine Levels in the Reward System

“…No differences in BECs were found between adolescents and adults following repeated ethanol administration, despite the differential magnitude in behavioral sensitization between them (Stevenson et al, 2008;Quoilin et al, 2012). Also, chronic ethanol pretreatment in adolescent and adult mice did not result in differential ALDH activity, although it had an impact on ethanol consumption patterns (Carrara-Nascimento et al, 2017). Despite these pieces of evidence, a study conducted by Linsenbardt et al (2009) demonstrated that adolescent mice exhibited lower BEC than adults after acute and chronic administration of 4.0 g/kg ethanol.…”

“…Although behavioral sensitization is not necessarily dependent on enhanced dopamine release in the striatum (Segal and Kuczenski, 1992), the expression of sensitization reflects, at least in part, neuroadaptations in the nigrostriatal dopaminergic pathway (Kalivas and Stewart, 1991). Thus, elevated dopamine striatal levels in adults repeatedly treated with ethanol can be, at least in part, responsible for their higher sensitivity to express ethanol-induced behavioral sensitization compared to adolescents (Faria et al, 2008;Stevenson et al, 2008;Carrara-Nascimento et al, 2014;Carrara-Nascimento et al, 2017).…”

Effects of environmental enrichment upon ethanol-induced conditioned place preference and pre-frontal BDNF levels in adolescent and adult mice

“…DBA/2 J mice, however, exhibited a negative correlation between ethanol intake and ethanol-induced CPP 45 , whereas pre-exposure to ethanol potentiates ethanol conditioning in the Swiss mice 46 . Adolescent Swiss mice also show, when compared to adult counterparts, lower levels of sensitization to ethanol 6 yet after the sensitization ethanol intake escalates more pronounced in the adolescents than in the adults 47 , Studies with the outbred strain OF1 have shown that pre-exposure to ethanol or to stress during adolescence enhances subsequent cocaine-induced CPP 48 and ethanol self-administration 49 , respectively. These studies, however, did not have an adult control group for comparison.…”

Primed for addiction: A critical review of the role of microglia in the neurodevelopmental consequences of adolescent alcohol drinking

“…Furthermore, valid comparisons between ages requires comparable BALs. There is some evidence of faster rates of EtOH clearance in adolescent animals, but the presence of significant pharmacokinetic differences varies widely across routes of administration, species, strains, and sex (Walker & Ehlers, 2009; Watson et al, 2020, but see Carrara‐Nascimento et al, 2017; Fleming et al, 2019; Lacaille et al, 2015; Morris et al, 2010b; Silveri & Spear, 2000; Vore et al, 2021). Importantly, where EtOH metabolism differences were observed, adolescents typically showed quicker clearance and therefore lower BALs despite greater pharmacodynamic effects.…”