2011
DOI: 10.1111/j.1369-1600.2011.00333.x View full text |Buy / Rent full text
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Abstract: The α4βδ gamma-aminobutyric acid A receptor (GABAAR) has been proposed to mediate the rewarding effects of low-to-moderate concentrations of alcohol (ethanol) that approximate those achieved by social drinking. If this is true, then this receptor should be necessary for the reinforcing effects of ethanol as assessed in an instrumental self-administration procedure in which rats are trained to lever press for oral ethanol. We used viral-mediated RNA interference to transiently reduce expression of the α4 GABAAR… Show more

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“…However, the ventral striatal region, the NAc, is required for PIT for alcohol cues (Corbit et al, 2016), and this region is also implicated in the direct reinforcing effects of alcohol (Englemann et al 2009; Rewal et al, 2012); it is not clear whether or how dependence upon the NAc for PIT or alcohol reinforcement in may change over time.…”
Section: Mechanismsmentioning
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“…However, the ventral striatal region, the NAc, is required for PIT for alcohol cues (Corbit et al, 2016), and this region is also implicated in the direct reinforcing effects of alcohol (Englemann et al 2009; Rewal et al, 2012); it is not clear whether or how dependence upon the NAc for PIT or alcohol reinforcement in may change over time.…”
Section: Mechanismsmentioning
“…It is unlikely that transient effects from a single exposure contribute to withdrawal effects, as synaptosomal changes occurred when blood ethanol are known to be greater than 300 mg/dL as we have reported elsewhere (see: Carter et al, in press ). GABA A receptor α4 knockout mice displayed normal behavioral responsivity to acute ethanol exposure (Chandra et al, 2008); however, viral-mediated knockdown of α4 subunit levels in the nucleus accumbens shell reveals that α4 expression impacts ethanol operant responding (Rewal et al, 2012). Given that thalamic extrasynaptic α4-containing GABA A receptors mediate tonic inhibitory currents that are potentiated at socially relevant ethanol concentrations (Chandra et al , 2008; Jia et al , 2008), reducing the number of ethanol sensitive receptors is likely a rapid mechanism to ameliorate ethanol’s increased central nervous system inhibition and behavioral responses.…”
Section: Discussionmentioning
“…Neurosteroids may also interfere with cocaine-induced associative learning, having important implications for cue-associated reinstatement [72,73]. The latest published research indicates that extrasynaptic GABA A receptors may be especially important in modulating tonic and reward-related dopamine within the mesolimbic circuit [74][75][76][77][78], which supports a role for neurosteroids in these effects since extrasynaptic GABA A receptors are a sensitive target for allopregnanolone and THDOC [75,77,79,80].…”
Section: Introductionmentioning