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. 2014 Sep 2:8:301.
doi: 10.3389/fnbeh.2014.00301. eCollection 2014.

Habitual responding for alcohol depends upon both AMPA and D2 receptor signaling in the dorsolateral striatum

Laura H Corbit  1 , Hong Nie  2 , Patricia H Janak  3
Affiliations

Habitual responding for alcohol depends upon both AMPA and D2 receptor signaling in the dorsolateral striatum

Laura H Corbit et al. Front Behav Neurosci. .

Abstract

Chronic alcohol self-administration leads to alcohol-seeking behavior that is habitual and insensitive to changes in the value of the earned alcohol. Such behavior has been shown to rely on the dorsolateral region of the striatum in rats but the specific pharmacological control of output from this region is not yet understood. In the following experiments rats were trained to self-administer unsweetened 10% (v/v) ethanol in daily sessions for 8 weeks prior to testing for sensitivity to outcome devaluation. We examined the role of glutamatergic AMPA-receptor activation by testing the effects of the antagonist NBQX (0.3 and 1.0 μg/μl) infused specifically into the dorsolateral striatum (DLS) before devaluation testing. In a separate group of rats we examined the role of dopaminergic D2-receptor activation using the D2-receptor antagonist raclopride (0.2 and 1.0 μg/μl) infused into the DLS before devaluation testing. Following control (saline) infusions rats' lever-press performance was insensitive to devaluation of ethanol thus showing evidence of habitual responding. NBQX and racolpride each restored goal-directed control of responding at doses that did not impair overall lever-press rates. These data demonstrate that expression of habitual alcohol seeking relies on glutamatergic inputs to the DLS and D2 receptors within the DLS.

Keywords: devaluation; dopamine; dorsal striatum; glutamate; habit learning; rat.

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Figures

Figure 1
Figure 1
Cannula placements within the DLS. Schematic representation of cannulae placements in the DLS for animals included in the NBQX (open circles) and raclopride (black circles) experiments (templates adapted from Paxinos and Watson, 1998). Numbers indicate the distance from bregma in anterior–posterior plane. N = 11 and 12 for NBQX and raclopride experiments, respectively.
Figure 2
Figure 2
Training data. (A) Mean (+/−SEM) lever presses, (B) outcomes earned, and (C) g/kg alcohol across weeks of instrumental training prior to devaluation testing.
Figure 3
Figure 3
Effects of NBQX infusion into the DLS on sensitivity to outcome devaluation. (A) Following 8 weeks of ethanol self-administration lever-press responding was insensitive to devaluation following saline infusions. Infusion of 0.3 μg/μl NBQX restored sensitivity to devaluation. Infusion of the higher dose (1.0 μg/μl) produced a marginal devaluation effect but overall responding was also lower. * indicates p < 0.05. (B) Mean magazine entries during the devaluation tests which show a similar pattern to lever-press performance.
Figure 4
Figure 4
Effects of NBQX on sensitivity of consumption to outcome devaluation and on home cage drinking. (A) When consumption of ethanol following pre-feeding of ethanol (devalued) or sucrose (non-devalued) was measured, a significant devaluation was detected demonstrating that the specific satiety treatment itself was effective but that this change in outcome value was not translated into lever-press performance under control conditions (see saline condition in Figure 3). (B) Ethanol consumption in the home cage following infusion of either saline or 0.3 μg/μl NBQX was equivalent indicating that NBQX treatment itself did not somehow change the rats’ willingness to consume ethanol. * indicates p < 0.05.
Figure 5
Figure 5
Effects of raclopride infusion into the DLS on sensitivity to outcome devaluation. (A) Following 8 weeks of ethanol self-administration lever-press responding was insensitive to devaluation following saline infusions. Infusion of the 0.2 μg/μl dose of raclopride restored sensitivity to devaluation. After infusion of the higher dose (1.0 μg/μl) sensitivity to devaluation was again lost. * indicates p < 0.05. (B) Mean magazine entries during the devaluation tests.
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