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The effects of age at the onset of drinking to intoxication and chronic ethanol self-administration in male rhesus macaques.

ABSTRACT: Consumption of alcohol begins during late adolescence in a majority of humans, and the greatest drinking occurs at 18-25 years then decreases with age.The present study measured the differences in ethanol intake in relation to age at the onset of ethanol access among nonhuman primates to control for self-selection in humans and isolate age effects on heavy drinking.Male rhesus macaques were assigned first access to ethanol during late adolescence (n?=?8), young adulthood (n?=?8), or early middle age (n?=?11). The monkeys were induced to drink ethanol (4 %?w/v in water) in increasing doses (water then 0.5, 1.0, 1.5 g/kg ethanol) using a fixed-time (FT) 300-s schedule of food delivery, followed by 22 h/day concurrent access to ethanol and water for 12 months. Age-matched controls consumed isocaloric maltose-dextrin solution yoked to the late adolescents expected to be rapidly maturing (n?=?4).Young adult monkeys had the greatest daily ethanol intake and blood-ethanol concentration (BEC). Only late adolescents escalated their intake (ethanol, not water) during the second compared to the first 6 months of access. On average, plasma testosterone level was consistent with age differences in maturation and tended to increase throughout the experiment more for control than ethanol-drinking adolescent monkeys.Young adulthood in nonhuman primates strongly disposes toward heavy drinking, which is independent of sociocultural factors present in humans. Ethanol drinking to intoxication during the critical period of late adolescence is associated with escalation to heavy drinking.

SUBMITTER: Helms CM

PROVIDER: S-EPMC3969395 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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The effects of age at the onset of drinking to intoxication and chronic ethanol self-administration in male rhesus macaques.

Helms Christa M CM Rau Andrew A Shaw Jessica J Stull Cara C Gonzales Steven W SW Grant Kathleen A KA

Psychopharmacology 20140122 8

<h4>Rationale</h4>Consumption of alcohol begins during late adolescence in a majority of humans, and the greatest drinking occurs at 18-25 years then decreases with age.<h4>Objectives</h4>The present study measured the differences in ethanol intake in relation to age at the onset of ethanol access among nonhuman primates to control for self-selection in humans and isolate age effects on heavy drinking.<h4>Methods</h4>Male rhesus macaques were assigned first access to ethanol during late adolesce ...[more]

PMID: 24448900

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Project description:Alcohol use disorder (AUD) is a devastating psychiatric disorder that has significant wide-reaching effects on individuals and society. Selectively bred mouse lines are an effective means of exploring the genetic and neuronal mechanisms underlying AUD and such studies are translationally important for identifying treatment options. Here, we report on behavioral characterization of two replicate lines of mice that drink to intoxication, the High Drinking in the Dark (HDID)-1 and -2 mice, which have been selectively bred (20+ generations) for the primary phenotype of reaching high blood alcohol levels (BALs) during the drinking in the dark (DID) task, a binge-like drinking assay. Along with their genetically heterogenous progenitor line, Hs/Npt, we tested these mice on: DID and drinking in the light (DIL); temporal drinking patterns; ethanol sensitivity, through loss of righting reflex (LORR); and operant self-administration, including fixed ratio (FR1), fixed ratio 3:1 (FR3), extinction/reinstatement, and progressive ratio (PR). All mice consumed more ethanol during the dark than the light and both HDID lines consumed more ethanol than Hs/Npt during DIL and DID. In the dark, we found that the HDID lines achieved high blood alcohol levels early into a drinking session, suggesting that they exhibit front loading like drinking behavior in the absence of the chronicity usually required for such behavior. Surprisingly, HDID-1 (female and male) and HDID-2 (male) mice were more sensitive to the intoxicating effects of ethanol during the dark (as determined by LORR), while Hs/Npt (female and male) and HDID-2 (female) mice appeared less sensitive. We observed lower HDID-1 ethanol intake compared to either HDID-2 or Hs/Npt during operant ethanol self-administration. There were no genotype differences for either progressive ratio responding, or cue-induced ethanol reinstatement, though the latter is complicated by a lack of extinguished responding behavior. Taken together, these findings suggest that genes affecting one AUD-related behavior do not necessarily affect other AUD-related behaviors. Moreover, these findings highlight that alcohol-related behaviors can also differ between lines selectively bred for the same phenotype, and even between sexes within those same line.

Dataset Information

The effects of age at the onset of drinking to intoxication and chronic ethanol self-administration in male rhesus macaques.

Publications

The effects of age at the onset of drinking to intoxication and chronic ethanol self-administration in male rhesus macaques.

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