Ethanol Exposure History and Alcoholic Reward Differentially Alter Dopamine Release in the Nucleus Accumbens to a Reward-Predictive Cue

Abstract

Background: Conditioned stimuli (CS) that predict reward delivery acquire the ability to induce phasic dopamine release in the nucleus accumbens (NAc). This dopamine release may facilitate conditioned approach behavior, which often manifests as approach to the site of reward delivery (called "goal-tracking") or to the CS itself (called "sign-tracking"). Previous research has linked sign-tracking in particular to impulsivity and drug self-administration, and addictive drugs may promote the expression of sign-tracking. Ethanol (EtOH) acutely promotes phasic release of dopamine in the accumbens, but it is unknown whether an alcoholic reward alters dopamine release to a CS. We hypothesized that Pavlovian conditioning with an alcoholic reward would increase dopamine release triggered by the CS and subsequent sign-tracking behavior. Moreover, we predicted that chronic intermittent EtOH (CIE) exposure would promote sign-tracking while acute administration of naltrexone (NTX) would reduce it.

Methods: Rats received 14 doses of EtOH (3 to 5 g/kg, intragastric) or water followed by 6 days of Pavlovian conditioning training. Rewards were a chocolate solution with or without 10% (w/v) alcohol. We used fast-scan cyclic voltammetry to measure phasic dopamine release in the NAc core in response to the CS and the rewards. We also determined the effect of NTX (1 mg/kg, subcutaneous) on conditioned approach.

Results: Both CIE and alcoholic reward, individually but not together, associated with greater dopamine to the CS than control conditions. However, this increase in dopamine release was not linked to greater sign-tracking, as both CIE and alcoholic reward shifted conditioned approach from sign-tracking behavior to goal-tracking behavior. However, they both also increased sensitivity to NTX, which reduced goal-tracking behavior.

Conclusions: While a history of EtOH exposure or alcoholic reward enhanced dopamine release to a CS, they did not promote sign-tracking under the current conditions. These findings are consistent with the interpretation that EtOH can stimulate conditioned approach, but indicate that the conditioned response may manifest as goal-tracking.

Keywords: Alcohol; Dopamine; Extinction; Naltrexone; Pavlovian.

Figure 1

Day-by-day timeline of the study. Note that day 42 of the study is Day 6 of Pavlovian conditioning training and day 43 of the study is Day 7 of training (the extinction session).

Figure 2

Both history of alcohol exposure and alcoholic reward affect dopamine transients at the onset of the CS, but not at delivery of the US reward. Bars represent mean ± SEM of the change in dopamine concentration, Δ[DA], occurring within 3 s of the onset of the CS (A) or the delivery of the US reward (B). * Within treatment group, ALC significantly different from ENS. # Within reward group, CIE significantly different from CON. CON, control exposure; CIE, chronic intermittent ethanol; ENS, nonalcoholic reward; ALC, alcoholic reward.

Figure 3

Individual examples of electrochemical signals at the CS onset as well as group-averaged traces of dopamine concentration over time: (A) CON-ENS, (B) CON-ALC, (C) CIE-ENS, and (D) CIE-ALC. The top of each panel shows a concentration-time trace and a color plot from an individual rat (all trials averaged), with arrows indicating the CS onset. The trace depicts concentration across the 10-s window at the peak oxidation potential of dopamine (∼0.65 V versus the Ag/AgCl reference electrode). The color plot indicates the current (color) over time (x-axis) at each applied potential (y-axis) for the same rat data as the trace above. Below the individual example, the average concentration across the 10-s window for the group is depicted as mean (filled line) and SEM (dashed gray line), and CS onset is represented by the green vertical line. Note the different concentration scale bars across groups. CON, control exposure; CIE, chronic intermittent ethanol; ENS, nonalcoholic reward; ALC, alcoholic reward.

Figure 4

Site of recording electrodes (circles) in the nucleus accumbens core of rats. Coordinates of coronal slices are approximate locations anterior to bregma (in mm), based on the Paxinos and Watson (1998) rat brain atlas.