title: Synaptic and morphological neuroadaptations in the putamen associated with long-term, relapsing alcohol drinking in primates.
abstract: Alcoholism and alcohol use disorders are characterized by several months to decades of heavy and problematic drinking, interspersed with periods of abstinence and relapse to heavy drinking. This alcohol-drinking phenotype was modeled using macaque monkeys to explore neuronal adaptations in the striatum, a brain region controlling habitual behaviors. Prolonged drinking with repeated abstinence narrowed the variability in daily intake, increased the amount of ethanol consumed in bouts, and led to higher blood ethanol concentrations more than twice the legal intoxication limit. After the final abstinence period of this extensive drinking protocol, we found a selective increase in dendritic spine density and enhanced glutamatergic transmission in the putamen, but not in the caudate nucleus. Intrinsic excitability of medium-sized spiny neurons was also enhanced in the putamen of alcohol-drinking monkeys in comparison with non-drinkers, and GABAeric transmission was selectively suppressed in the putamen of heavy drinkers. These morphological and physiological changes indicate a shift in the balance of inhibitory/excitatory transmission that biases the circuit toward an enduring increase in synaptic activation of putamen output as a consequence of prolonged heavy drinking/relapse. The resultant potential for increased putamen activation may underlie an alcohol-drinking phenotype of regulated drinking and sustained intoxication.
authors.affiliation: Laboratory for Integrative Neuroscience, Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, MD, USA.
authors.forename: Verginia C
authors.initials: VC
authors.lastname: Cuzon Carlson
authors.forename: Gail K
authors.initials: GK
authors.lastname: Seabold
authors.forename: Christa M
authors.initials: CM
authors.lastname: Helms
authors.forename: Natasha
authors.initials: N
authors.lastname: Garg
authors.forename: Misa
authors.initials: M
authors.lastname: Odagiri
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Rau
authors.forename: James
authors.initials: J
authors.lastname: Daunais
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Alvarez
authors.forename: David M
authors.initials: DM
authors.lastname: Lovinger
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Grant
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000428:Alcohol Drinking / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage; D008252:Macaca fascicularis; D008297:Male; D011699:Putamen / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D012008:Recurrence; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors
chemical_list: D000431:Ethanol