5 research outputs found

    Protracted motivational dopamine-related deficits following adolescence sugar overconsumption

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    Adolescence represents a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system during adolescence might constitute an important factor of vulnerability to pathological development. Increasing evidences suggest that adolescent overconsumption of sweet palatable foods impact reward-based processes. However, the neurobiological bases of these deficits remain poorly understood. Previous studies have demonstrated motivational deficits for palatable foods after sweet diet exposure during adolescence that might involve the dopamine (DA) system, a central actor in incentive processes. In the present study, the impact of adolescent sugar overconsumption on the sensitivity of the DA system was tested using pharmacological (Experiment 1) and receptor expression approaches (Experiment 2). Adolescent rats received free and continuous access to 5% sucrose solution from post-natal day 30-46. At adulthood, the functionality of the DA system in motivational processes was tested using systemic injections of specific DA receptors D1R or D2R agonists and antagonists during a motivation-dependent progressive ratio task (Experiment 1). Sucrose-exposed rats showed a lower motivation for saccharin and a decreased sensitivity to the effects of both D1R and D2R stimulation and blockade. In Experiment 2, Sucrose-exposed animals presented a lower expression of both D1R and D2R in the nucleus accumbens, a central brain region for incentive processes, but not in dorsal striatum or prefrontal cortex. These findings highlight the impact of sucrose overconsumption during adolescence on DA system that may support deficits in reward-related disorders

    A Role for Medial Prefrontal Dopaminergic Innervation in Instrumental Conditioning

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    To investigate the involvement of dopaminergic projections to the prelimbic and infralimbic cortex in the control of goal-directed responses, a first experiment examined the effect of pretraining 6-OHDA lesions of these cortices. We used outcome devaluation and contingency degradation procedures to separately assess the representation of the outcome as a goal or the encoding of the contingency between the action and its outcome. All groups acquired the instrumental response at a normal rate, indicating that dopaminergic activity in the medial prefrontal cortex is not necessary for the acquisition of instrumental learning. Sham-operated animals showed sensitivity to both outcome devaluation and contingency degradation. Animals with dopaminergic lesions of the prelimbic cortex, but not the infralimbic cortex, failed to adapt their instrumental response to changes in contingency, whereas their response remained sensitive to outcome devaluation. In a second experiment, aimed at determining whether dopamine was specifically needed during contingency changes, we performed microinfusions of the dopamine D(1)/D(2) receptor antagonist flupenthixol in the prelimbic cortex only before contingency degradation sessions. Animals with infusions of flupenthixol failed to adapt their response to changes in contingency, thus replicating the deficit of animals with dopaminergic lesions in Experiment 1. These results demonstrate that dissociable neurobiological mechanisms support action-outcome relationships and goal representation, dopamine signaling in the prelimbic cortex being necessary for the former but not the latter

    Parallel Maturation of Goal-Directed Behavior and Dopaminergic Systems during Adolescence

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    Adolescence is a crucial developmental period characterized by specific behaviors reflecting the immaturity of decision-making abilities. However, the maturation of precise cognitive processes and their neurobiological correlates at this period remain poorly understood. Here, we investigate whether a differential developmental time course of dopamine (DA) pathways during late adolescence could explain the emergence of particular executive and motivational components of goal-directed behavior. First, using a contingency degradation protocol, we demonstrate that adolescent rats display a specific deficit when the causal relationship between their actions and their consequences is changed. When the rats become adults, this deficit disappears. In contrast, actions of adolescents remain sensitive to outcome devaluation or to the influence of a pavlovian-conditioned stimulus. This aspect of cognitive maturation parallels a delayed development of the DA system, especially the mesocortical pathway involved in action adaptation to rule changes. Unlike in striatal and nucleus accumbens regions, DA fibers and DA tissue content continue to increase in the medial prefrontal cortex from juvenile to adult age. Moreover, a sustained overexpression of DA receptors is observed in the prefrontal region until the end of adolescence. These findings highlight the relationship between the emergence of specific cognitive processes, in particular the adaptation to changes in action consequences, and the delayed maturation of the mesocortical DA pathway. Similar developmental processes in humans could contribute to the adolescent vulnerability to the emergence of several psychiatric disorders characterized by decision-making deficits
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