Corticostriatal Oscillations Predict High vs. Low Drinkers in a Rat Model of Limited Access Alcohol Consumption

Abstract

Individuals differ in their vulnerability to develop alcohol dependence, which is determined by innate and environmental factors. The corticostriatal circuit is heavily involved in the development of alcohol dependence and may contain neural information regarding vulnerability to drink excessively. In the current experiment, we hypothesized that we could characterize high and low alcohol-drinking rats (HD and LD, respectively) based on corticostriatal oscillations and that these subgroups would differentially respond to corticostriatal brain stimulation. Male Sprague-Dawley rats (n = 13) were trained to drink 10% alcohol in a limited access paradigm. In separate sessions, local field potentials (LFPs) were recorded from the nucleus accumbens shell (NAcSh) and medial prefrontal cortex (mPFC). Based on training alcohol consumption levels, we classified rats using a median split as HD or LD. Then, using machine-learning, we built predictive models to classify rats as HD or LD by corticostriatal LFPs and compared the model performance from real data to the performance of models built on data permutations. Additionally, we explored the impact of NAcSh or mPFC stimulation on alcohol consumption in HD vs. LD. Corticostriatal LFPs were able to predict HD vs. LD group classification with greater accuracy than expected by chance (>80% accuracy). Moreover, NAcSh stimulation significantly reduced alcohol consumption in HD, but not LD (p < 0.05), while mPFC stimulation did not alter drinking behavior in either HD or LD (p > 0.05). These data collectively show that the corticostriatal circuit is differentially involved in regulating alcohol intake in HD vs. LD rats, and suggests that corticostriatal activity may have the potential to predict a vulnerability to develop alcohol dependence in a clinical population.

Keywords: alcohol; brain stimulation; local field potentials; medial prefrontal cortex; nucleus accumbens.

Figure 1

Experimental timeline.

Figure 2

Categorization of rats as high or low alcohol drinkers (HD or LD). Average g/kg of alcohol consumed for HD and LD was significantly different across the 12 training sessions, prior to stimulation (F_(1,11) = 5.86, p = 0.03, $n_{\text{p}}^2$ = 0.35; A). Average g/kg of alcohol consumed across the last 3 days of alcohol drinking training was significantly different between HD and LD (t₍₁₁₎ = 5.79, p = 0.00; B; n = 6–7/group).

Figure 3

Prediction model. Corticostriatal local field potential (LFP) oscillations predict HD vs. LD better than permuted data (permuted μ = 48 ± 1%; real μ = 80 ± 2%; n = 10–14/group; A). A sample trace of corticostriatal LFP oscillations used in the prediction model (B). Histology figures representing electrode placements in the nucleus accumbens shell (NAcSh; C) and medial prefrontal cortex (mPFC; D) from Bregma.

Figure 4

Response to 130 Hz NAcSh and mPFC stimulation. NAcSh stimulation led to a significant decrease in alcohol consumption from training (pre-stimulation) to the stimulation sessions in the HD only (F_(1,11) = 5.89, p = 0.03, $n_{\text{p}}^2$ = 0.35; A). Panels (B,C) represent the individual responses to NAcSh stimulation in HD and LD, respectively. Neither HD or LD showed a significant change in alcohol consumption due to mPFC stimulation (F_(1,10) = 0.04, p = 0.85, $n_{\text{p}}^2$ = 0.00; D). Panels (E,F) represent the individual responses to mPFC stimulation in HD and LD, respectively (n = 5–7/group). Asterisk denotes a significant change of p < 0.05.