Biology subjects

Vouillac-Mendoza, C.

Publications and source records attributed to Vouillac-Mendoza, C..

5 recordsLinked to original sources

bioRxiv2024

Distinct neuronal processes in the ventromedial prefrontal cortex mediate changes in attention load and nicotine pro-cognitive effects

The prefrontal cortex (PFC) plays a key role in attention. In particular, neuronal activity in the ventromedial PFC (vmPFC) has been implicated in the preparatory attentional period that immediately precedes cue presentation. However, whether vmPFC neuronal activity during this preparatory period is also sensitive to changes in task demand and to the pro-cognitive effects of nicotine remained to be investigated. Here, we used in vivo electrophysiology to record vmPFC neuronal activity during two distinct manipulations: a task manipulation that increased task demand by reducing the cue stimulus duration (from 1s to 0.5s), and a pharmacological manipulation by administrating an acute nicotine injection (10 {micro}g/inj, i.v.) before the session. We found that increasing task demand decreased attentional performances and vmPFC precue neuronal activity, but had no effect on gamma oscillations. In contrast, nicotine injection increased attention and gamma oscillations, but almost abolished vmPFC phasic precue responses. Together, these findings indicate the existence of two distinct neuronal mechanisms operating at different timescales and suggests that allocation of attention could be achieved through multiple complementary neuronal mechanisms within the vmPFC.

neuroscience↗

bioRxiv2023

Bidirectional relationship between attentional deficits and escalation of nicotine intake

Smoking addicts have deficits in cognition, in particular deficits in attention, even long after smoking cessation. It is not clear however, whether deficits are a cause or a consequence, or both, of chronic nicotine use. Here we set out a series of experiments in rats to address this question and, more specifically, to assess the long-term effects of exposure to and withdrawal from chronic nicotine self-administration on attentional performance. Animals were trained in a 5-choice serial reaction time task to probe individual attentional performance and, then, were given access to a fixed versus increasing dose of intravenous nicotine for self-administration, a differential dose procedure known to induce two between-session patterns of nicotine intake: a stable versus escalation pattern. Attentional performance was measured daily before, during and also 24-h after chronic access to the differential dose procedure of nicotine self-administration. We found that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake. Moreover, while chronic nicotine self-administration increases attention, withdrawal from nicotine intake escalation induces attentional deficits, a withdrawal effect that is dose-dependently reversed by acute nicotine. Together, these results suggest that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake, and that part of the motivation for using nicotine during escalation might be to alleviate withdrawal-induced attentional deficits.

neuroscience↗

bioRxiv2022

Large-scale brain correlates of sweet versus cocaine reward in rats

Cocaine induces many supranormal changes in neuronal activity in the brain, notably in learning- and reward-related regions, in comparison to nondrug rewards - a difference that is thought to contribute to its relatively high addictive potential. However, when facing a choice between cocaine and a nondrug reward (e.g., water sweetened with saccharin), most rats do not choose cocaine, as one would expect from the extent and magnitude of its global activation of the brain, but instead choose the nondrug option. We recently showed that cocaine, though larger in magnitude, is also an inherently more delayed reward than sweet water, thereby explaining why it has less value during choice and why rats opt for the more immediate nondrug option. Here we used a large-scale fos brain mapping approach to measure brain responses to each option in saccharin-preferring rats, with the hope to identify brain regions whose activity may explain the preference for the nondrug option. In total, fos expression was measured in 142 brain levels corresponding to 52 brain subregions and composing 5 brain macrosystems. Overall, our findings confirm in rats with a preference for saccharin that cocaine induces more global brain activation than the preferred nondrug option does. Only very few brain regions were uniquely activated by saccharin. They included regions involved in taste processing (i.e., anterior gustatory cortex) and also regions involved in processing reward delay and intertemporal choice (i.e., some components of the septohippocampal system and its connections with the lateral habenula).

neuroscience↗

bioRxiv2020

Probing the decision-making mechanisms underlying choice between drug and nondrug rewards in rats

Investigating the decision-making mechanisms underlying choice between drug and nondrug rewards is essential to understand how their alterations can contribute to substance use disorders. However, despite some recent effort, this investigation remains a challenge in a drug choice setting, notably when it comes to delineate the role of goal-directed versus habitual control mechanisms. The goal of this study was to try probing these different mechanisms by comparing response latencies measured during sampling (i.e., only one option is available) and choice trials. A deliberative goal-directed control mechanism predicts a lengthening of latencies during choice whereas a habitual control mechanism predicts no change in latencies. Alternatively, a race-like response competition mechanism, such as that postulated by the behavioral ecology-inspired Sequential Choice Model (SCM), predicts instead a shortening of response latencies during choice compared to sampling. Here we tested the predictions of these different mechanisms by conducting a systematic retrospective analysis of all cocaine versus saccharin choice experiments conducted in rats in our laboratory over the past 12 years. Overall, we found that rats engage a deliberative goal-directed mechanism after limited training, but shift to a SCM-like response selection mechanism after more extended training. The latter finding suggests that habitual control is engaged in a choice setting via a race-like response competition mechanism, and thus, that the SCM is not a general model of choice, as formulated initially, but a specific model of habitual choice.

animal behavior and cognition↗

bioRxiv2020

Pharmacokinetics trumps pharmacodynamics during cocaine choice: a reconciliation with the dopamine hypothesis of addiction

Cocaine is known to increase brain dopamine at supranormal levels in comparison to alternative nondrug rewards. According to the dopamine hypothesis of addiction, this difference would explain, at least in part, why the latter are eventually given up in favor of continued cocaine use during the transition to addiction. Though resting on solid neuroscientific foundations, this hypothesis has nevertheless proven difficult to reconcile with research on cocaine choice in experimental animals. When facing a choice between an intravenous bolus of cocaine and a nondrug alternative (e.g., sweet water), both delivered immediately after choice, rats do not choose the drug, as would be predicted, but instead develop a strong preference for the nondrug alternative, sometimes to the exclusion of continued drug use. Here we report converging evidence that reconciles this finding with the dopamine hypothesis of addiction. Briefly, our data suggest that cocaine is indeed supranormal in reward magnitude, as postulated by the dopamine hypothesis of addiction, but is less preferred during choice because its pharmacokinetics makes it an inherently more delayed reward than the alternative. Reframing previous drug choice studies in rats as intertemporal choice studies reveals that the discounting effects of delays spare no rewards, including supranormal ones, and that during choice, pharmacokinetics trumps pharmacodynamics. Finally, this study also reveals important gaps in our understanding of drug reward delays that need to be filled by future experimental and theoretical work.

neuroscience↗