Biology subjects

Baunez, C.

Publications and source records attributed to Baunez, C..

6 recordsLinked to original sources

bioRxiv2023

Social Context and Drug Cues Modulate Inhibitory Control in Cocaine Addiction: involvement of the STN evidenced through Functional Magnetic Resonance Imaging

BackgroundAddictions often develop in a social context, although the influence of social factors did not receive much attention in the neuroscience of addiction. Recent animal studies suggest that peer presence can reduce cocaine intake, an influence potentially mediated, among others, by the subthalamic nucleus (STN). However, there is to date no such neurobiological study in humans. MethodsThis study investigated the impact of social context and drug cues on brain correlates of inhibitory control in individuals with and without cocaine use disorder (CUD) using functional Magnetic Resonance Imaging (fMRI). Seventeen CUD participants and 17 healthy controls (HC) performed a novel fMRI Stop-Signal task in the presence and absence of an observer while being exposed to cocaine-related and neutral pictures as cues. ResultsThe results showed that CUD participants, while slower at stopping with neutral cues, recovered control level stopping abilities with cocaine cues, while HC did not show any difference. Neuroimaging revealed the involvement of frontal cortical regions and of the subthalamic nucleus (STN) in inhibitory control, which was modulated by both social context and drug cues in CUD participants but not in HC. ConclusionsThese findings highlight the impact of social context and drug cues on inhibitory control in CUD and suggest potential targets for intervention such as the STN, also emphasizing the importance of considering the social context in addiction research and treatment.

neuroscience↗

bioRxiv2023

Peer's Presence Reverses Escalated Cocaine Intake In Rats

The immediate social context critically modulates drug consumption. The presence of an unfamiliar conspecific, naive to the drug, at the time of consumption reduces cocaine self-administration in male rats during short-access sessions, as well as drug intake in human cocaine users. The subthalamic nucleus (STN), a brain structure involved in cocaine addiction and limbic processes, has been proposed to mediate such social influence on this limited level of drug intake. Whether this influence extends to escalated drug consumption remains an open question. In this study, we compared the effect of the presence of an unfamiliar peer, naive to cocaine, on cocaine self-administration in rats having been exposed to either short (2h) or long-access sessions (6h). We showed that the presence of the peer drastically reduced both limited and escalated cocaine intake in males, while it had no effect on females during short-access sessions. Assessing the effect of STN photo-inhibition or high frequency (HF) stimulation in male rats, we demonstrated that it had no effect in the absence of the conspecific in short-access sessions, STN photo-manipulation suppressed the influence of the peers presence. Moreover, STN photo-inhibition and HF stimulation decreased drug consumption in long-access sessions, but no additive effect was observed when associated with the peers presence, confirming an overriding effect of STN manipulation. Taken together, these results highlight the potential influence of socially oriented manipulations on cocaine intake and further position the STN as a critical mediator of the effect of social presence on addictive-like behaviors.

neuroscience↗

bioRxiv2021

Decision-Making in Rats is Sensitive to Rare and Extreme Events: the Black Swan Avoidance

Most behavioral studies in animals investigate risk using outcome probabilities larger than 10%. However, real-world Decision-Making often requires evaluating events that are both extremely unlikely and highly consequential. To address this gap, we developed an experimental and computational framework to quantify how rats detect and adapt to rare (probability <1%) and extreme (deviation from mean >10 standard deviations) outcomes (REE). Using a four-armed bandit task, animals chose between options associated with probabilistic rewards (sugar pellets) or punishments (time-out delays). Depending on the animals choice, REE can occur or not, allowing us to probe how rats integrate information across both common and fat-tailed event distributions. Across subjects, behavior showed restricted diversification (typically two out of four options) and clear sensitivity to REE, expressed as a systematic avoidance of rare and extreme punishments (Black Swans) combined with partial exposure to rare and extreme gains (Jackpots). The dominant behavioral phenotype displayed a near-complete suppression of exposure to Black Swans, whereas exposure to Jackpots remained only moderate. This asymmetric sensitivity came at a cost: these animals accepted smaller frequent gains and larger frequent losses to avoid catastrophic outcomes. To account for these behaviors, we implemented an augmented reinforcement learning model in which REE are weighted separately from frequent events. Fitting this model to individual behavioral data captured subjects decision patterns far better than standard Q-learning, which systematically failed to reproduce the observed asymmetry. The best-fitting model suggests that the rat brain segregates information from the central outcome distribution and the distribution tails, assigning distinct value weights to REE during action selection. This work provides the first evidence that rodents spontaneously adapt their learning strategies to avoid extreme punishments while partially maintaining exposure to rare and extreme gains, suggesting that frequent outcomes are treated separately from rare and extreme ones through different weights in Decision-Making.

animal behavior and cognition↗

bioRxiv2018

Subthalamic nucleus optogenetic manipulations: a glimpse at deep brain stimulation mechanisms

Although deep brain stimulation (DBS) is now a widely used therapeutic strategy, its precise mechanism remains largely unclear. Since this approach is progressively extended to treat non-motor disorders such as depression, obsessive-compulsive disorders, the comprehension of its effects on motivated behaviors appears of the upmost importance for a possible application for addiction. In intact rats, we used inhibition and high frequency optogenetic activation of subthalamic nucleus (STN) neurons to test whether or not we could reproduce the effects of electric deep brain stimulation on rats motivation for sweet food and cocaine. Rats motivation was assessed using fixed-ratio 5 and progressive ratio schedules of reinforcement for both rewards and illumination was applied during behavioral testing. Efficiency of optogenetic manipulations has been validated using in-vitro electrophysiological recordings. Optogenetic inhibition of STN increased motivation for food and reduced motivation for cocaine. In contrast, optogenetic high frequency stimulation reduced the motivation for food without impacting motivation for cocaine. Optical inhibition mimics the effect of electric deep brain stimulation on food and cocaine motivation, confirming that the effects observed under electric DBS result from a specific inactivation of the STN. In contrast, optogenetic high frequency stimulation induces opposite effects to those of electric one, suggesting a stimulation of the STN that only seems to affect food motivation.

neuroscience↗

bioRxiv2018

Reversing compulsive cocaine seeking with low frequency deep brain stimulation of the subthalamic nucleus

Cocaine seeking despite a foot-shock contingency is used to model compulsive drug seeking, a core component of drug addiction, in rodents. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is efficient on other addiction criteria models and we show here that 30-Hz STN stimulation reduces pathological cocaine seeking in compulsive-like rats. This confirms STN DBS as a potential strategy to treat addiction. We also observed that only compulsive-like rats displayed a progressive increase in STN low frequency oscillations, especially in the alpha/theta band (6-13 Hz), during cocaine escalation. Conversely, applying 8-Hz STN DBS to mimic alpha/theta oscillations in non-compulsive animals changed them into compulsive ones. We have thus identified a predictive neuronal biomarker of compulsivity. Since one critical challenge in addiction research is to identify vulnerable individuals before they transition to harmful drug consumption pattern, our results could lead to new diagnostic tools and prevention strategies.

neuroscience↗

bioRxiv2018

Of Rats And Men: Peer Presence And Familiarity Are Key Factors Which Modulate Drug Intake

Social environment influences drug consumption, its persistence and evolution. Little is known regarding the influence of the presence of a peer during drug consumption and especially how the relationship between peers (familiarity and dominance) can influence drug consumption. We used here a translational and transdisciplinary approach to explore the influence of peer presence and peer familiarity in rats and humans that self-administer stimulants. In rats, cocaine intake was compared when rats were alone with intake when peers with different characteristics (familiar or not, cocaine naive or not, dominant or subordinate) were present. In humans, 77 cocaine and/or methylphenidate users were asked to detail their most recent drug use episodes and their relationship with peers present at consumption. The results show that in both humans and rats, the risk of cocaine/stimulant consumption was significantly reduced by 37% and 32%, respectively, when a peer was present. Moreover, the lowest risk of consumption was consistently observed when the peer was unfamiliar (vs familiar) with a further 38% and 17% risk reduction, respectively. In rats, a decreased risk of consumption was greater when the peer was cocaine naive (vs non-cocaine naive).\n\nThe presence of a non-familiar and possibly drug-naive peer is the most efficient condition to diminish stimulant intake. Our results indirectly support the use of harm reduction strategies, in particular supervised consumption rooms for stimulant users.

neuroscience↗