4.7 Article

Synaptic adaptations to chronic ethanol intake in male rhesus monkey dorsal striatum depend on age of drinking onset

期刊

NEUROPHARMACOLOGY
卷 131, 期 -, 页码 128-142

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2017.12.010

关键词

Caudate; Putamen; Adolescent drinking; Adult drinking; Non-human primate; Whole-cell patch clamp electrophysiology

资金

  1. Division of Intramural Clinical and Biological Research NIAAA [ZIA AA 000407]
  2. Integrative Neuroscience Initiative on Alcoholism [U01 AA13510]
  3. Monkey Alcohol Tissue Research Resource [R24 AA019431]
  4. INIA Administrative Core [U24 AA13641]
  5. [P51 OD 011092]

向作者/读者索取更多资源

One in 12 adults suffer with alcohol use disorder (AUD). Studies suggest the younger the age in which alcohol consumption begins the higher the probability of being diagnosed with AUD. Binge/excessive alcohol drinking involves a transition from flexible to inflexible behavior likely involving the dorsal striatum (caudate and putamen nuclei). A major focus of this study was to examine the effect of age of drinking onset on subsequent chronic, voluntary ethanol intake and dorsal striatal circuitry. Data from rhesus monkeys (n = 45) that started drinking as adolescents, young adults or mature adults confirms an age-related risk for heavy drinking. Striatal neuroadaptations were examined using whole-cell patch clamp electrophysiology to record AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and GABAA receptor-mediated miniature inhibitory postsynaptic currents (mEPSCs) from medium-sized spiny projection neurons located in the caudate or putamen nuclei. In controls, greater GABAergic transmission (mIPSC frequency and amplitude) was observed in the putamen compared to the caudate. With advancing age, in the absence of ethanol, an increase in mIPSC frequency concomitant with changes in mIPSC amplitude was observed in both regions. Chronic ethanol drinking decreased mIPSC frequency in the putamen regardless of age of onset. In the caudate, an ethanol drinking-induced increase in mIPSC frequency was only observed in monkeys that began drinking as young adults. Glutamatergic transmission did not differ between the dorsal striatal subregions in controls. With chronic ethanol drinking there was a decrease in the postsynaptic characteristics of rise time and area of mEPSCs in the putamen but an increase in mEPSC frequency in the caudate. Together, the observed changes in striatal physiology indicate a combined disinhibition due to youth and ethanol leading to abnormally strong activation of the putamen that could contribute to the increased risk for problem drinking in younger drinkers. Published by Elsevier Ltd.

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