Dysfunction in striatal dopaminergic and oxytocinergic system on impulsive choice behavior
Fecha
2021Autor
Fuentealba-Evans, José Antonio
PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE
Institución
Resumen
A key measure of impulsive choice involves a preference for smaller but immediately delivered reinforcements versus larger rewards associated with delayed delivery. This behavior is present in several neuropsychiatric disorders, including personality disorders, attention deficit disorder, hyperactivity, and addiction. In recent years it has been proposed that all of these pathologies share an alteration in mesencephalic dopaminergic transmission, but the physiological mechanisms that accompany the expression of impulsive choice are not fully clarified. Moreover, recent findings suggest that oxytocin (OXT) can modulate several behaviors related to the dopaminergic system and a bidirectional modulation between them. The present study aimed to investigate: (1) The basal dopaminergic dynamics in the dorsolateral striatum (DLS) present in individual differences of impulsive choice behaviors. (2) The role of the oxytocinergic system on nigro-striatal dopaminergic transmission and its modulation in impulsive choice behaviors.
The results showed that: (1) Dopamine (DA) release in DLS is higher in highly impulsive animals (HI) than in low impulsive animals (LI). However, DA extracellular (DAext) ext levels and transporter activity (DAT) do not vary between groups. (2) The bilateral activation of OXT-R in substantia nigra pars compacta (SNpc) induces a decrease in impulsive behavior, in animals previously classified as HI. Moreover, the OXT-R activation in SNpc induces a modest increase in DAext in DLS. This finding shows that DA release is augmented in the DLS of rats classified as HI, suggesting that hyper-activity nigro-striatal pathway contributes to impulsive choice. On the other hand, the activation of the OXT-R in the SNpc influences delay- related decision making by subtle changes in the striatal dopamine transmission. These results propose a new line of research on the neurobiological mechanisms underlying the possible interaction between the OXT and DA systems and their role in impulsive choice behaviors present in pathologies associated with altering these two systems in the nigrostriatal pathway.