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.
Highlights
MATERIALS AND METHODSSome characteristics of the adolescence have been related to delayed maturation of prefrontal cortex and neurotransmitter systems as well as late development of behavioral inhibitory systems, which may render adolescents especially vulnerable to taking drugs of abuse and developing addiction (Spear, 2000; Chambers et al, 2003)
We showed that both adolescent and adult mice treated with 2.0 g/kg ethanol (Adolescent-EtOH and Adult-EtOH) displayed ethanol behavioral sensitization and that adolescents were less sensitive than adults, which is in agreement with studies from our laboratory and others (Stevenson et al, 2008; Quoilin et al, 2012; Soares-Simi et al, 2013; Carrara-Nascimento et al, 2014)
The most striking result is that Adolescent-EtOH but not Adult-EtOH displayed escalated amounts of 4% ethanol intake during acquisition and maintained higher ethanol intake than Adult-EtOH after repeated withdrawals and reexposures, even when ethanol solution was adulterated with quinine or
Summary
MATERIALS AND METHODSSome characteristics of the adolescence (impulsivity, risky behavior, seeking of new experiences) have been related to delayed maturation of prefrontal cortex and neurotransmitter systems as well as late development of behavioral inhibitory systems, which may render adolescents especially vulnerable to taking drugs of abuse and developing addiction (Spear, 2000; Chambers et al, 2003). The main route of ethanol elimination is the liver metabolism, where it is converted into acetaldehyde by alcohol dehydrogenase and subsequently to acetate by aldehyde dehydrogenase (ALDH). Those enzymes are responsible for the elimination of alcohol in concentrations below 20 mmol/L (Li, 1977; Lieber, 1986). Recent data of our group suggested that adult but not adolescent mice developed metabolic tolerance to increases in blood ethanol concentration induced by chronic intermittent ethanol exposure (Carrara-Nascimento et al, 2013), suggesting that the age of exposure to ethanol may influence ethanol metabolism
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