Browsing by Author "Novoa, Javier"

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    Reactive oxygen species modulate locomotor activity and dopamine extracellular levels induced by amphetamine in rats
    (2022) Zegers-Delgado, Juan; Blanlot, Camila; Calderon, Florencia; Yarur, Hector E.; Novoa, Javier; Vega-Quiroga, Ignacio; Bastias, Cristian P.; Gysling, Katia
    The increase of dopamine (DA) in the reward system is related to the reinforcing effects of drugs of abuse and hyper locomotion induced by psychostimulants. The increase of DA induced by drugs of abuse generates high amounts of ROS by monoamines metabolization. It has been showed that ROS could modulate psychomotor response and reinforcing effects induced by drugs of abuse as cocaine and methamphetamine (METH). The aim of this study is to evaluate the relation of ROS and amphetamine (AMPH). Here, we show that pretreatment of the ROS scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) attenuates the induction of locomotion and oxidative stress generated in nucleus accumbens (Nac) by acute AMPH administration. Interestingly, TEMPOL also attenuates the increase of DA induced by AMPH in Nac. Finally, TEMPOL reduces DAT phosphorylation when AMPH is co-infused in Nac synaptosomes. Taking together, our results suggest that ROS modulate AMPH effects in rats.
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    Social isolation of adolescent male rats increases anxiety and K+-induced dopamine release in the nucleus accumbens: Role of CRF-R1
    (2021) Novoa, Javier; Rivero, Carlos J.; Perez-Cardona, Enrique U.; Freire-Arvelo, Jaime A.; Zegers, Juan; Yarur, Hector E.; Santiago-Marerro, Ivan G.; Agosto-Rivera, Jose L.; Gonzalez-Perez, Jorge L.; Gysling, Katia; Segarra, Annabell C.
    Early life adversity can disrupt development leading to emotional and cognitive disorders. This study investigated the effects of social isolation after weaning on anxiety, body weight and locomotion, and on extracellular dopamine (DA) and glutamate (GLU) in the nucleus accumbens (NAc) and their modulation by corticotropin releasing factor receptor 1. On the day of weaning, male rats were housed singly or in groups for 10 consecutive days. Anxiety-like behaviors were assessed by an elevated plus maze (EPM) and an open field test (OF). Neurotransmitter levels were measured by in vivo microdialysis. Single-housed rats spent less time, and entered more, into the closed arms of an EPM than group-housed rats. They also spent less time in the center of an OF, weighed more and showed greater locomotion. In the NAc, no differences in CRF, or in basal extracellular DA or GLU between groups, were observed. A depolarizing stimulus increased DA release in both groups but to higher levels in isolated rats, whereas GLU increased only in single-housed rats. Blocking CRF-R1 receptors with CP-154,526 decreased DA release in single-housed but not in group-housed rats. The corticotropin releasing factor receptor type 1 receptor antagonist also decreased GLU in group-housed animals. These results show that isolating adolescent rats increases anxiety, body weight and ambulation, as well as the sensitivity of dopaminergic neurons to a depolarizing stimulus. This study provides further evidence of the detrimental effects of social isolation during early development and indicates that dysregulation of the CRF system in the NAc may contribute to the pathologies observed.
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    Type 1 Corticotropin-Releasing Factor Receptor Differentially Modulates Neurotransmitter Levels in the Nucleus Accumbens of Juvenile versus Adult Rats
    (2022) Zegers-Delgado, Juan; Aguilera-Soza, Alejandro; Calderon, Florencia; Davidson, Harley; Verbel-Vergara, Daniel; Yarur, Hector E.; Novoa, Javier; Blanlot, Camila; Bastias, Cristian P.; Estela Andres, Maria; Gysling, Katia
    Adversity is particularly pernicious in early life, increasing the likelihood of developing psychiatric disorders in adulthood. Juvenile and adult rats exposed to social isolation show differences in anxiety-like behaviors and significant changes in dopamine (DA) neurotransmission in the nucleus accumbens (NAc). Brain response to stress is partly mediated by the corticotropin-releasing factor (CRF) system, composed of CRF and its two main receptors, CRF-R1 and CRF-R2. In the NAc shell of adult rats, CRF induces anxiety-like behavior and changes local DA balance. However, the role of CRF receptors in the control of neurotransmission in the NAc is not fully understood, nor is it known whether there are differences between life stages. Our previous data showed that infusion of a CRF-R1 antagonist into the NAc of juvenile rats increased DA levels in response to a depolarizing stimulus and decreased basal glutamate levels. To extend this analysis, we now evaluated the effect of a CRF-R1 antagonist infusion in the NAc of adult rats. Here, we describe that the opposite occurred in the NAc of adult compared to juvenile rats. Infusion of a CRF-R1 antagonist decreased DA and increased glutamate levels in response to a depolarizing stimulus. Furthermore, basal levels of DA, glutamate, and gamma-Aminobutyric acid (GABA) were similar in juvenile animals compared to adults. CRF-R1 protein levels and localization were not different in juvenile compared to adult rats. Interestingly, we observed differences in the signaling pathways of CRF-R1 in the NAc of juveniles compared to adult rats. We propose that the function of CRF-R1 receptors is differentially modulated in the NAc according to life stage.