Binge-Like Alcohol Exposure During Adolescence Disrupts Dopaminergic Neurotransmission in the Adult Prelimbic Cortex.
Repeated binge-like exposure to alcohol during adolescence has been reported to perturb prefrontal cortical development, yet the mechanisms underlying these effects are unknown. Here we report that adolescent intermittent ethanol exposure induces cellular and dopaminergic abnormalities in the adult prelimbic cortex (PrL-C). Exposing rats to alcohol during early-mid adolescence (PD28-42) increased the density of long/thin dendritic spines of layer 5 pyramidal neurons in the adult PrL-C. Interestingly, although AIE exposure did not alter the expression of glutamatergic proteins in the adult PrL-C, there was a pronounced reduction in dopamine (DA) D1receptor modulation of both intrinsic firing and evoked NMDA currents in pyramidal cells, whereas D2receptor function was unaltered. Recordings from fast-spiking interneurons also revealed that AIE reduced intrinsic excitability, glutamatergic signaling, and D1receptor modulation of these cells. Analysis of PrL-C tissue of AIE-exposed rats further revealed persistent changes in the expression of DA-related proteins, including reductions in the expression of tyrosine hydroxylase and catechol-O-methyltransferase (COMT). AIE exposure was associated with hypermethylation of the COMT promoter at a conserved CpG site in exon II. Taken together, these findings demonstrate that AIE exposure disrupts DA and GABAergic transmission in the adult medial prefrontal cortex (mPFC). As DA and GABA work in concert to shape and synchronize neuronal ensembles in the PFC, these alterations could contribute to deficits in behavioral control and decision-making in adults who abused alcohol during adolescence.
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Heather
H
Trantham-Davidson
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Samuel W
SW
Centanni
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
S Corrin
SC
Garr
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Natasha N
NN
New
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Patrick J
PJ
Mulholland
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Justin T
http://orcid.org/0000-0002-6829-6261
JT
Gass
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Elizabeth J
EJ
Glover
Department of Psychology and Brain Research Centre, University of British Columbia, Vancouver, BC, Canada.
Stan B
SB
Floresco
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Fulton T
FT
Crews
Department of Psychiatry, University of Illinois at Chicago and Jesse Brown VA Medical Center, Chicago, IL, USA.
Harish R
HR
Krishnan
Department of Psychiatry, University of Illinois at Chicago and Jesse Brown VA Medical Center, Chicago, IL, USA.
Subhash C
SC
Pandey
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
L Judson
LJ
Chandler
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000502:physiology; D011954:Receptors, Dopamine / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018091:Receptors, AMPA; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D014446:Tyrosine 3-Monooxygenase; D002394:Catechol O-Methyltransferase; D004298:Dopamine