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

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.

Peer presence and familiarity as key factors to reduce cocaine intake in both rats and humans: an effect mediated by the subthalamic nucleus.

RATIONALE: Stimulant use, including cocaine, often occurs in a social context whose influence is important to understand to decrease intake and reduce associated harms. Although the importance of social influence in the context of drug addiction is known, there is a need for studies assessing its neurobiological substrate and for translational research. OBJECTIVES: Here, we explored the influence of peer presence and familiarity on cocaine intake and its neurobiological basis. Given the regulatory role of the subthalamic nucleus (STN) on cocaine intake and emotions, we investigated its role on such influence of social context on cocaine intake. METHODS: We first compared cocaine consumption in various conditions (with no peer present or with peers with different characteristics: abstinent peer or drug-taking peer, familiar or not, cocaine-naive or not, dominant or subordinate) in rats (n = 90). Then, with a translational approach, we assessed the influence of the social context (alone, in the group, in a dyad with familiar or non-familiar peers) on drug intake in human drug users (n = 77). RESULTS: The drug consumption was reduced when a peer was present, abstinent, or drug-taking as well, and further diminished when the peer was non-familiar. The presence of a non-familiar and drug-naive peer represents key conditions to diminish cocaine intake. The STN lesion by itself reduced cocaine intake to the level reached in presence of a non-familiar naive peer and affected social cognition, positioning the STN as one neurobiological substrate of social influence on drug intake. Then, the human study confirmed the beneficial effect of social presence, especially of non-familiar peers. CONCLUSION: Our results indirectly support the use of social interventions and harm reduction strategies and position the STN as a key cerebral structure to mediate these effects.

Evidence for a vocal signature in the rat and its reinforcing effects: a key role for the subthalamic nucleus.

Although rodents have a well-structured vocal form of communication, like humans and non-human primates, there is, to date, no evidence for a vocal signature in the well-known 50- and 22-kHz ultrasonic vocalizations (USVs) emitted by rats. Here, we show that rats can recognize the identity of the USV emitter since they choose to preferentially self-administer playback of 50-kHz USVs emitted by a stranger rat over those of their cagemate. In a second experiment, we show that only stranger, but not familiar, 50-kHz USVs reduce cocaine self-administration. Finally, to study the neurobiological substrate of these processes, we have shown that subthalamic nucleus (STN)-lesioned rats did not lever press much for any USV playback, whatever their emotional valence, nor did they seem able to differentiate familiar from stranger peer. Advocating for the existence of a vocal signature in rats, these results highlight the importance of ultrasonic communication in the socio-affective influence of behaviour, such as the influence of proximal social factors on drug consumption and confirm the role of the STN on this influence.

Repeated cocaine exposure prior to fear conditioning induces persistency of PTSD-like symptoms and enhancement of hippocampal and amygdala cell density in male rats.

Pre- and post-trauma drug use can interfere with recovery from post-traumatic stress disorder (PTSD). However, the biological underpinnings of this interference are poorly understood. Here we examined the effect of pre-fear conditioning cocaine self-administration on PTSD-like symptoms in male rats, and defined impairment of fear extinction as difficulty to recover from PTSD. We also examined cell density changes in brain regions suspected of being involved in resistance to PTSD recovery. Before footshock stress testing, rats were trained to self-administer cocaine during 20 consecutive days, after which they were exposed to footshocks, while other rats continued to self-administer cocaine until the end of the experiment. Upon assessment of three PTSD-like symptoms (fear during situational reminders, anxiety-like behavior, and impairment of recognition memory) and fear extinction learning and memory, changes in cell density were measured in the medial prefrontal cortex, hippocampus, and amygdala. Results show that pre-footshock cocaine exposure did not affect fear during situational reminders. Fear conditioning did not lead to an increase in cocaine consumption. However, in footshock stressed rats, cocaine induced a reduction of anxiety-like behavior, an aggravation of recognition memory decline, and an impairment of extinction memory. These behavioral alterations were associated with increased cell density in the hippocampal CA1, CA2, and CA3 regions and basolateral amygdala, but not in the medial prefrontal cortex. Our findings suggest that enhancement of cell density in the hippocampus and amygdala may be changes associated with drug use, interfering with PTSD recovery.