Repeated administration of psychostimulant drugs induces a long-term state of sensitization in the mesolimbic dopamine system. This hyperdopaminergic state is associated with enhanced reward-seeking behaviors. Such aberration of incentive motivational processing is suggested to facilitate the initiation and maintenance of compulsive drug-taking behaviors. A defining characteristic of addiction is the persistence to pursue drug reinforcement despite negative consequences associated with administration. Thus, it is likely that addicts frequently experience states of motivational conflict to both seek and avoid the drug. The present study investigated the effects of repeated cocaine exposure on goal-seeking behaviors in rats, utilizing conflict paradigms wherein positive and negative incentive motivations were simultaneously evoked. Here it was shown that cocaine-experienced rats displayed both enhanced approach and avoidance behaviors, depending upon the conditions put forth in each paradigm. The results contribute to elucidating the consequences of drug administration upon basic motivational processes that may influence compulsive drug-taking behaviors.

Repeated administration of psychostimulant drugs induces a long-term state of sensitization in the mesolimbic dopamine system. This hyperdopaminergic state is associated with enhanced reward-seeking behaviors. Such aberration of incentive motivational processing is suggested to facilitate the initiation and maintenance of compulsive drug-taking behaviors. A defining characteristic of addiction is the persistence to pursue drug reinforcement despite negative consequences associated with administration. Thus, it is likely that addicts frequently experience states of motivational conflict to both seek and avoid the drug. The present study investigated the effects of repeated cocaine exposure on goal-seeking behaviors in rats, utilizing conflict paradigms wherein positive and negative incentive motivations were simultaneously evoked. Here it was shown that cocaine-experienced rats displayed both enhanced approach and avoidance behaviors, depending upon the conditions put forth in each paradigm. The results contribute to elucidating the consequences of drug administration upon basic motivational processes that may influence compulsive drug-taking behaviors.

Rationale. Adolescence may be a period of susceptibility to the effects of drugs of abuse. This vulnerability may result from a convergence of psychological processes that contribute to drug addiction including impulsive action and incentive motivation during adolescence. Objectives. I examined age differences in incentive motivation, as measured by responding for a conditioned reinforcer (CR) previously paired with natural or drug rewards, and age and sex differences in impulsive action, as measured by responding on a differential reinforcement of low rates of responding (DRL) schedule or premature responding on the 2-Choice Serial Reaction Time Test (2-CSRTT), in Sprague-Dawley rats. The effects of drugs that affect these behaviours in adulthood and that act on neurochemical systems still developing during adolescence were also examined. Methods. In a first set of experiments (Chapter 3), I compared male adolescents and adults on responding for a CR previously paired with sucrose and the effect of amphetamine on this behaviour. In a second set of experiments (Chapter 4), I examined age differences in responding for a CR previously paired with passive or self-administered intravenous (IV) nicotine infusions. Subsequently, I investigated age and sex differences in responding on a DRL schedule in response to amphetamine (Chapter 5) and 2-CSRTT performance in response to amphetamine, nicotine and Ro 63-1908 (a glutamate N-Methyl-D-aspartic acid [NMDA] receptor subunit antagonist; Chapter 6). Results. Compared to adults, adolescents responded more for a CR previously paired with sucrose or passive, but not self-administered, IV nicotine infusions. Amphetamine only enhanced responding for a CR previously paired with sucrose. Adolescents responded more than adults on a DRL schedule, while adolescents made the most premature responses in the 2-CSRTT. No consistent sex differences were observed during the acquisition of either behaviour. Amphetamine increased premature responding most in adolescent males and adult females in the 2-CSRTT but not in responding on the DRL schedule. No consistent age or sex differences were observed for Ro 63-1908 or nicotine. Conclusions. Adolescents show enhanced impulsivity and incentive motivation than adults depending on the behavioural measure. Dopamine may contribute to age and sex differences in these behaviours.

La symptomatologie non motrice de la maladie de Parkinson s’accompagne fréquemment d’un défaut de contrôle cognitif. Le contrôle cognitif faisant référence à un ensemble de processus facilitant le traitement de l’information et la production de comportements adaptés, son altération impactera de très nombreuses capacités cognitives. Parmi ces capacités, nous nous intéresserons plus spécifiquement, d’une part, à la production orale de mots évaluée à travers les tests de fluences verbales et, d’autre part, aux processus favorisant la production d’actions intentionnelles en situation motivée comme évaluée par la Simon Task motivée. Par notre première étude nous remettrons en question l’hypothèse d’un défaut de contrôle cognitif comme origine principale de la réduction des performances aux tests de fluences verbales à la suite de la stimulation cérébrale profonde du noyau subthalamique. En effet, nous n’avons pas mis en évidence de relation entre cette altération et une modification de l’activité métabolique des régions frontales supportant le contrôle cognitif, ou une modification des performances à d’autres tests nécessitant un contrôle cognitif efficient. Les travaux suivant, portant sur le contrôle des actions motivées démontrent, d’une part, que la production d’actions guidées, non pas par des tendances d’actions impulsives, mais par des tendances d’actions en accord avec les intentions, est plus ardue lorsqu’une récompense financière est mise en jeu. D’autre part, le traitement de la maladie de Parkinson, aussi bien par dopathérapie que par stimulation cérébrale profonde du noyau sous-thalamique module le fonctionnement des processus impliqués, suggérant un rôle particulier des noyaux gris centraux. Nous discuterons des processus cognitifs et neuronaux impliqués et proposerons des perspectives de recherche aussi bien neuroscientifiques que cliniques. / The nonmotor symptoms of Parkinson’s disease frequently include a cognitive control deficit. Cognitive control refers to a set of processes that promote information processing and the production of appropriate behaviours, so its impairment can have an impact on a wide range of cognitive abilities. We focused on just two of these abilities: oral word production, as assessed with phonemic and semantic verbal fluency tests; and cognitive action control in an incentive context, as assessed with a rewarded Simon Task. In our first study, we questioned the hypothesis that the reduction in verbal fluency performances observed following surgery for subthalamic nucleus deep-brain stimulation is mainly due to a cognitive control deficit. Results failed to reveal a relationship between this reduction and either modified metabolic activity in the frontal regions subtending cognitive control or modified performances on other tests requiring efficient cognitive control. In our second and third studies, investigating cognitive action control in an incentive context, we showed that the production of intention-driven actions, as opposed to impulsive ones, is more difficult when a monetary reward is at stake. We also demonstrated that treatment for Parkinson’s disease, whether it takes the form of dopaminergic medication or subthalamic stimulation, modulates the functioning of these processes, suggesting that the basal ganglia have a role in them. We discuss the cognitive and neural processes involved and outline future avenues for both neuroscientific and clinical research.

We recently showed that incentive motivation improves the precision of the Approximate Number System (ANS) in young adults. To shed light on the development of incentive motivation, the present study investigated whether this effect and its underlying mechanisms may also be observed in younger samples. Specifically, seven-year-old children (n = 23; 12 girls) and 14-year-old adolescents (n = 30; 15 girls) performed a dot comparison task with monetary reward incentives. Both age groups showed higher accuracy in a reward compared to a neutral condition and, similarly, higher processing efficiency as revealed by the drift rate parameter of the EZ-diffusion model. Furthermore, in line with the Incentive Salience Hypothesis, phasic pupil dilations—indicating the activation of the brain’s salience network—were greater in incentivized trials in both age groups. Together these finding suggest that incentive modulation improves numerosity discrimination in children and adolescents by enhancing the perceptual saliency of numerosity information. However, the observed reward anticipation effects were less pronounced in children relative to adolescents. Furthermore, unlike previous findings regarding young adults, the decision thresholds of children and adolescents were not raised by the monetary reward, which may indicate a more protracted development of incentive regulation of response caution than perceptual evidence accumulation.