title: Greater ethanol-induced locomotor activation in DBA/2J versus C57BL/6J mice is not predicted by presynaptic striatal dopamine dynamics.
abstract: A large body of research has aimed to determine the neurochemical factors driving differential sensitivity to ethanol between individuals in an attempt to find predictors of ethanol abuse vulnerability. Here we find that the locomotor activating effects of ethanol are markedly greater in DBA/2J compared to C57BL/6J mice, although it is unclear as to what neurochemical differences between strains mediate this behavior. Dopamine elevations in the nucleus accumbens and caudate-putamen regulate locomotor behavior for most drugs, including ethanol; thus, we aimed to determine if differences in these regions predict strain differences in ethanol-induced locomotor activity. Previous studies suggest that ethanol interacts with the dopamine transporter, potentially mediating its locomotor activating effects; however, we found that ethanol had no effects on dopamine uptake in either strain. Ex vivo voltammetry allows for the determination of ethanol effects on presynaptic dopamine terminals, independent of drug-induced changes in firing rates of afferent inputs from either dopamine neurons or other neurotransmitter systems. However, differences in striatal dopamine dynamics did not predict the locomotor-activating effects of ethanol, since the inhibitory effects of ethanol on dopamine release were similar between strains. There were differences in presynaptic dopamine function between strains, with faster dopamine clearance in the caudate-putamen of DBA/2J mice; however, it is unclear how this difference relates to locomotor behavior. Because of the role of the dopamine system in reinforcement and reward learning, differences in dopamine signaling between the strains could have implications for addiction-related behaviors that extend beyond ethanol effects in the striatum.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Jamie H
authors.initials: JH
authors.lastname: Rose
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Erin S
authors.initials: ES
authors.lastname: Calipari
authors.affiliation: Department of Chemistry, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Mathews
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Jones
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects*; D017729:Presynaptic Terminals / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D004298:Dopamine