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Social rank, chronic ethanol self-administration, and diurnal pituitary-adrenal activity in cynomolgus monkeys.

ABSTRACT: Dominance hierarchies affect ethanol self-administration, with greater intake among subordinate animals compared to dominant animals. Excessive ethanol intake disrupts circadian rhythms. Diurnal rhythms of the hypothalamic-pituitary-adrenal axis have not been characterized in the context of ethanol self-administration with regard to social rank.This study aimed to determine whether diurnal pituitary-adrenal hormonal rhythms account for differences between social ranks in ethanol self-administration or are differentially affected by ethanol self-administration between social ranks.During alternating individual (n?=?11-12) and social (n?=?3 groups) housing of male cynomolgus monkeys (Macaca fascicularis), diurnal measures of cortisol and adrenocorticotropic hormone (ACTH) were obtained from plasma samples three times per week. Social rank was determined, ethanol (4 %, w/v) self-administration was induced, and then the monkeys were allowed a choice of water or ethanol for 22 h/day for 49 weeks.For all social ranks, plasma ACTH was elevated during social housing, but cortisol was stable, although greater among dominant monkeys. Ethanol self-administration blunted the effect of social housing, cortisol, and the diurnal rhythm for both hormones, regardless of daily ethanol intake (1.2-4.2 g/kg/day). Peak ACTH and cortisol were more likely to be observed in the morning during ethanol access. Ethanol, not vehicle, intake was lower during social housing across social ranks. Only dominant monkeys showed significantly lower blood-ethanol concentration during social housing.There was a low threshold for disruption of diurnal pituitary rhythms by ethanol drinking, but sustained adrenal corticosteroid rhythms. Protection against heavy drinking among dominant monkeys may have constrained ethanol intoxication, possibly to preserve dominance rank.

SUBMITTER: Helms CM

PROVIDER: S-EPMC3469782 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Social rank, chronic ethanol self-administration, and diurnal pituitary-adrenal activity in cynomolgus monkeys.

Helms Christa M CM McClintick Megan N MN Grant Kathleen A KA

Psychopharmacology 20120418 1

<h4>Rationale</h4>Dominance hierarchies affect ethanol self-administration, with greater intake among subordinate animals compared to dominant animals. Excessive ethanol intake disrupts circadian rhythms. Diurnal rhythms of the hypothalamic-pituitary-adrenal axis have not been characterized in the context of ethanol self-administration with regard to social rank.<h4>Objective</h4>This study aimed to determine whether diurnal pituitary-adrenal hormonal rhythms account for differences between soci ...[more]

PMID: 22526537

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Project description:BackgroundFunctional impairment of the orbital and medial prefrontal cortex underlies deficits in executive control that characterize addictive disorders, including alcohol addiction. Previous studies indicate that alcohol alters glutamate neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting ionotropic glutamate receptor (iGluR) complexes. Glutamatergic transmission is integral to cortico-cortical and cortico-subcortical communication, and alcohol-induced changes in the abundance of the receptor subunits and/or their splice variants may result in critical functional impairments of prefrontal cortex in the alcohol-addicted state.Methods and resultsThe effects of chronic ethanol self-administration on glutamate receptor ionotropic NMDA (GRIN), as well as GRIN1 splice variant mRNA expression was studied in the orbitofrontal cortex (OFC; Area 13), dorsolateral prefrontal cortex (DLPFC; Area 46) and anterior cingulate cortex (ACC; Area 24) of male cynomolgus monkeys. Chronic ethanol self-administration resulted in significant changes in the expression of NMDA subunit mRNA expression in the DLPFC and OFC, but not the ACC. In DLPFC, the overall expression of NMDA subunits was significantly decreased in ethanol treated monkeys. Slight but significant changes were observed for synaptic associated protein 102 kD (SAP102) and neuronal nitric oxide synthase (nNOS) mRNAs. In OFC, the NMDAR1 variant GRIN1-1 was reduced while GRIN1-2 was increased. Furthermore, no significant changes in GFAP protein levels were observed in either the DLPFC or OFC.ConclusionResults from these studies provide the first demonstration of posttranscriptional regulation of iGluR subunits in the primate brain following long-term ethanol self-administration. Furthermore, changes in these transcripts do not appear to reflect changes in glial activation or loss. Further studies examining the expression and cellular localization of subunit proteins and receptor pharmacology would shed more light on the findings reported here.

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Dataset Information

Social rank, chronic ethanol self-administration, and diurnal pituitary-adrenal activity in cynomolgus monkeys.

Publications

Social rank, chronic ethanol self-administration, and diurnal pituitary-adrenal activity in cynomolgus monkeys.

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