title: Chronic alcohol disrupts dopamine receptor activity and the cognitive function of the medial prefrontal cortex.
abstract: Dopamine (DA) receptors in the medial prefrontal cortex (mPFC) exert powerful effects on cognition by modulating the balance between excitatory and inhibitory neurotransmission. The present study examined the impact of chronic intermittent ethanol (CIE) exposure on cognitive function and DA receptor-mediated neurotransmission in the rat mPFC. Consistent with alterations in executive function in alcoholics, CIE-exposed rats exhibited deficits in behavioral flexibility in an operant set-shifting task. Since alterations in dopaminergic neurotransmission in the mPFC have been implicated in a number of behavioral disorders including addiction, studies were then performed in the adult acute slice preparation to examine changes in DA receptor function in the mPFC following CIE exposure. In slices obtained from control rats, DA receptor stimulation was observed to exert complex actions on neuronal firing and synaptic neurotransmission that were not only dependent upon the particular receptor subtype but also whether it was a pyramidal cell or a fast-spiking interneuron. In contrast to slices from control rats, there was a near complete loss of the modulatory actions of D2/D4 receptors on cell firing and neurotransmission in slices obtained immediately, 1 and 4 weeks after the last day of CIE exposure. This loss did not appear to be associated with changes in receptor expression. In contrast, CIE exposure did not alter D1 receptor function or mGluR1 modulation of firing. These studies are consistent with the suggestion that chronic alcohol exposure disrupts cognitive function at least in part through disruption of D2 and D4 receptor signaling in mPFC.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425 and Department of Psychology and Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada V6T1Z4.
authors.forename: Heather
authors.initials: H
authors.lastname: Trantham-Davidson
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Burnett
authors.forename: Justin T
authors.initials: JT
authors.lastname: Gass
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Lopez
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Mulholland
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Centanni
authors.forename: Stan B
authors.initials: SB
authors.lastname: Floresco
authors.forename: L Judson
authors.initials: LJ
authors.lastname: Chandler
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D010775:Photic Stimulation / Q000379:methods; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000502:physiology; D050638:Receptors, Dopamine D4 / Q000819:agonists* / Q000502:physiology
chemical_list: D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D000431:Ethanol
keywords: D2/D4; PFC; alcohol; cognitive; dopamine; mGluR1