Subthalamic high-frequency deep brain stimulation reduces addiction-like alcohol use and the possible negative influence of a peer presence

Abstract

Rationale: The immediate social context significantly influences alcohol consumption in humans. Recent studies have revealed that peer presence could modulate drugs use in rats. The most efficient condition to reduce cocaine intake is the presence of a stranger peer, naive to drugs. Deep brain stimulation (DBS) of the Subthalamic Nucleus (STN), which was shown to have beneficial effects on addiction to cocaine or alcohol, also modulates the protective influence of peer's presence on cocaine use.

Objectives: This study aimed to: 1) explore how the presence of an alcohol-naive stranger peer affects recreational and escalated alcohol intake, and 2) assess the involvement of STN on alcohol use and in the modulation induced by the presence of an alcohol-naïve stranger peer.

Methods: Rats with STN DBS and control animals self-administered 10% (v/v) ethanol in presence, or absence, of an alcohol-naive stranger peer, before and after escalation of ethanol intake (observed after intermittent alcohol (20% (v/v) ethanol) access).

Results: Neither STN DBS nor the presence of an alcohol-naive stranger peer modulated significantly recreational alcohol intake. After the escalation procedure, STN DBS reduced ethanol consumption. The presence of an alcohol-naive stranger peer increased consumption only in low drinkers, which effect was suppressed by STN DBS.

Conclusions: These results highlight the influence of a peer's presence on escalated alcohol intake, and confirm the role of STN in addiction-like alcohol intake and in the social influence on drug consumption.

Keywords: Alcohol; Deep brain stimulation; Peer’s presence; Social context; Subthalamic nucleus.

Fig. 1

Timeline of the behavioral experiment. Top: Behavioral experiment timeline, Down: (left) schematic representations of the electrode implanted in the STN, (right) Picture from a representative electrode implanted in the STN (delineated by the red dashed line)

Fig. 2

Neither peer’s presence nor STN DBS modulate recreational ethanol intake. Results are presented as mean ± SEM number of rewards obtained (i.e. number of active lever presses) per 1 h-session. (a) Number of rewards obtained for non-STN-stimulated (black dots – OFF—control) and stimulated (red dots – ON) groups during five sessions in the alone condition (7.88 ± 0.29 vs. 7.60 ± 0.25 rewards respectively) and five sessions with an alcohol-naive stranger peer (8.36 ± 0.48 vs. 8.09 ± 0.15 rewards respectively) (b) Number of rewards obtained in control (black dots – OFF—control) and STN-stimulated (red dots – ON) High drinkers in the alone condition (10.95 ± 0.40 vs. 10.37 ± 0.40 rewards respectively) and in a presence of an alcohol-naive stranger peer (11.05 ± 0.72 vs. 9, 73 ± 0.53 rewards, respectively) (c) Number of rewards obtained in control (black dots – OFF—control) and stimulated (red dots—ON) Low drinkers in the alone condition (4.37 ± 0.23 vs. 5.23 ± 0.27 rewards, respectively) and in a presence of an alcohol-naive stranger peer (5.29 ± 0.39 vs. 6.69 ± 0.19 rewards, respectively)

Fig. 3

STN DBS reduces the escalated intake of alcohol and suppresses the increased consumption induced by the peer’s presence. Results are presented as mean ± SEM. (a) Ethanol intake in control (black dots—OFF) and “to be stimulated” (red dots – ON) groups across the 15 sessions of intermittent access to 20% ethanol. Both groups increased their consumption from session 1 (1.66 ± 0.13 g/kg ethanol) to session 15 (3.01 ± 0.35 g/kg ethanol). (b) Water intake in OFF (black dots—OFF) and “to be stimulated” (red dots—ON) groups across the 15 sessions of intermittent access to 20% ethanol. Both groups consumed the same amount of water between session 1 (16.22 ± 0.92 g/kg water) and session 15 (22.39 ± 2.27 g/kg water). (c) Number of rewards obtained after the loss of control of alcohol intake for non-stimulated (black dots – OFF—control) and STN-stimulated rats (red dots – ON) during five 1 h-sessions in the alone condition (9.30 ± 1.10 vs. 6.13 ± 0.55 rewards, respectively) and five 1 h-sessions with an alcohol-naive stranger peer (10.58 ± 1.08 vs. 5.63 ± 0.62 rewards, respectively) (d) Number of rewards obtained by the non-stimulated group and stimulated rats after reordering the sessions in the proper sequence irrespective of the social context. ANOVA revealed a general session and a group effect. (e) Number of rewards obtained in control (black dots – OFF—control) and STN-stimulated (red dots—ON) High Drinkers after a loss of control, in the alone condition (12.83 ± 1.59 vs. 9.48 ± 0.92 rewards respectively) and in a presence of an alcohol-naive stranger peer (12.69 ± 1.78 vs. 6.72 ± 1.15 rewards, respectively) (f) Number of rewards obtained in control (black dots – OFF—control) and stimulated (red dots – ON) Low Drinkers after a loss of control, in the alone condition (4.40 ± 0.42 vs. 3.74 ± 0.45 rewards, respectively) and in a presence of an alcohol-naive stranger peer (7.64 ± 0.34 vs. 4.86 ± 0.48 rewards, respectively) * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001 ### p < 0.001 between “alone” and “with peer” conditions in the non-stimulated (OFF—control) group