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Fitoussi, A. Y.

Publications and source records attributed to Fitoussi, A. Y..

2 recordsLinked to original sources

Poor decision-makers motivation, working memory performance, and repartition across two rat inbred strains

A minority of healthy individuals (poor decision-makers, PD) exhibit a combination of behavioral traits reminiscent, at least in part, of addiction and predicting poor decision-making (DM), namely motor impulsivity, inflexibility, risk-taking, and higher motivation in Wistar Han rats. Two behavioral features, motivation and working memory (WM), play a role in DM capacities although the precise relationship is not entirely known. Additionally, we previously reported that neurotransmitters e.g., dopamine - modulation was tightly linked to the PD phenotype. The goal of the study was to investigate the detailed motivational functions in PD individuals including saccharin intake, reward-seeking or incentive behaviors under different internal states i.e., food-deprived or ad libitum. Maze-based spatial WM was also evaluated. Moreover, two inbred strains of rats, Lewis and Fisher 344 (F344) rats, known for modeling vulnerability to drug addiction and affected by substantial variations in the mesolimbic dopaminergic pathway, were run in the DM task (Rat Gambling Task, RGT). PD Wistar Han rats displayed higher saccharin intake levels and a drastic increased reward-seeking behavior on a fixed schedule. PD were more sensitive to the internal state in responding to saccharin delivery in fixed but not in progressive schedules. A few relationships were found within motivational functions, and with DM, that is a positive correlation between saccharin intake and reward-seeking behavior, and a negative correlation between saccharin intake and DM. PD were significantly not impaired in WM. Lewis and F344 rats displayed improved performance early in the task (exploration) and a higher proportion of PD was observed in Lewis as compared to F344 rats. Altogether, these findings complete the preclinical panel of behavioral functions that relate to poor DM and extend a presumed role of dopamine in such processes.

neuroscience↗

Behavioral Phenotyping from deleted CB1 receptors on cholinergic neuron terminals

Marijuana is the most widely used illicit drug in the Western Hemisphere and affects physiological processes and cognition. Clear deficits are observed in working memory (WM) that involve the temporary storage and online manipulation of information to solve complex tasks. Marijuana-induced WM deficits have been ascribed to the primary psychoactive compound in marijuana, {Delta}9-tetrahydrocannabinol, which acts at CB1 cannabinoid receptors (CB1r). Recent work emphasized the role of CB1r and cholinergic interaction across this cognitive domain without formal anatomical demonstration. We generated mice with a conditional deletion of CB1r on cholinergic neuron terminals, and WM was evaluated in operant chambers. Control of physiological variables (temperature, nociception, neuromuscular function) was also performed, and additional motor, motivation, time estimation behavior, and effort-based decision-making. Discrete WM enhancement measured in a novel Delay-Non-Matching-To-Position task was evidenced that incorporates early acquisition during randomized delays (mixed procedure), and remarkably, improved performance when these (2s, 8s, 16s, 20s) were kept constant (same procedure) across a testing block of trials. We reported higher motivation in an exponential progressive ratio schedule whilst locomotor activity did not differ between genotypes in the rotarod and open field. However, timing behavior was modified as indicated by higher discriminated motor responses for the shortest interval in conditional deleted mice in the Fixed-Interval time task (10s, 30s). We reported no effect on effort-based decision-making. Our work outlines presynaptic CB1r-cholinergic neuron function(s), and the hippocampus, neocortex, and amygdala brain regions as critical loci through known basal forebrain efferent projections possibly involved in WM and motivation in marijuana intoxication.

neuroscience↗