Reactive oxygen species modulate locomotor activity and dopamine extracellular levels induced by amphetamine in rats

Zegers-Delgado, Juan; Blanlot, Camila; Calderon, F.; Yarur, Héctor E.; Nóvoa, Javier; Vega-Quiroga, Ignacio; Bastias, Cristian P.; Gysling, Katia

doi:10.1016/j.bbr.2022.113857

Cited by 3 publications

(4 citation statements)

References 20 publications

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“…This contrasts with the earlier truncated Immp2l Tg(Tyr)979Ove mouse that suggested loss of Immp2l activity was associated with an increase in ROS production and oxidative stress phenotypes including oxidative stress in the brain causing ataxia and neurodegeneration [ 3 , 28 , 29 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. Moreover, ROS has been implicated as a mediator of the effects of amphetamine on locomotion [ 100 ]. However, our data provide convincing evidence that ROS-mediated oxidative stress is not evident in the Immp2l KD −/− KO mouse model and that it is not involved in the behavioural changes that result from the loss of Immp2l activity in this model.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Behavioural Phenotype in the Immp2l Gene Knock-Out Mouse

Lawther,

Zieba,

Fang

et al. 2023

Genes

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Mitochondrial dysfunction is strongly associated with autism spectrum disorder (ASD) and the Inner mitochondrial membrane protein 2-like (IMMP2L) gene is linked to autism inheritance. However, the biological basis of this linkage is unknown notwithstanding independent reports of oxidative stress in association with both IMMP2L and ASD. To better understand IMMP2L’s association with behaviour, we developed the Immp2lKD knockout (KO) mouse model which is devoid of Immp2l peptidase activity. Immp2lKD −/− KO mice do not display any of the core behavioural symptoms of ASD, albeit homozygous Immp2lKD −/− KO mice do display increased auditory stimulus-driven instrumental behaviour and increased amphetamine-induced locomotion. Due to reports of increased ROS and oxidative stress phenotypes in an earlier truncated Immp2l mouse model resulting from an intragenic deletion within Immp2l, we tested whether high doses of the synthetic mitochondrial targeted antioxidant (MitoQ) could reverse or moderate the behavioural changes in Immp2lKD −/− KO mice. To our surprise, we observed that ROS levels were not increased but significantly lowered in our new Immp2lKD −/− KO mice and that these mice had no oxidative stress-associated phenotypes and were fully fertile with no age-related ataxia or neurodegeneration as ascertained using electron microscopy. Furthermore, the antioxidant MitoQ had no effect on the increased amphetamine-induced locomotion of these mice. Together, these findings indicate that the behavioural changes in Immp2lKD −/− KO mice are associated with an antioxidant-like phenotype with lowered and not increased levels of ROS and no oxidative stress-related phenotypes. This suggested that treatments with antioxidants are unlikely to be effective in treating behaviours directly resulting from the loss of Immp2l/IMMP2L activity, while any behavioural deficits that maybe associated with IMMP2L intragenic deletion-associated truncations have yet to be determined.

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Section: Discussionmentioning

confidence: 99%

Antioxidant Behavioural Phenotype in the Immp2l Gene Knock-Out Mouse

Lawther,

Zieba,

Fang

et al. 2023

Genes

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“…Electrophoresis was performed in a chamber filled with buffer (25 mM Tris-base, 192 mM Glycine, 10% SDS) using a constant voltage of 70 V for the first 30 min and then followed by a constant voltage of 100 V until the end of the proteins reached the end of the gel. Subsequently, proteins were transferred for 90 min at 300 mA while submerged in a cold buffer (25 mM Tris-base, 192 mM Glycine, 10% SDS, 20% methanol) onto a 45 µM methanol activated PVDF membrane attached to the gel via a transfer sandwich, following the methodology we previously used [86]. Once the transfer was completed, the membrane was blocked in a blocking solution (5% non-fat dry milk (Svelty), dissolved in 1 × −0.05% TBS solution of Tween 20) for 1 h with orbital shaking.…”

Section: Western Blotmentioning

confidence: 99%

“…Immunofluorescence was performed as previously described [86]. Briefly, animals were transcardially perfused with 4% paraformaldehyde.…”

Section: Immunofluorescencementioning

confidence: 99%

Type 1 Corticotropin-Releasing Factor Receptor Differentially Modulates Neurotransmitter Levels in the Nucleus Accumbens of Juvenile versus Adult Rats

Zegers-Delgado

Aguilera-Soza

Calderon

et al. 2022

IJMS

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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 γ-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.

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“…Other experimental studies that indicated a connection between ROS accumulation and substance abuse in rodents include non-specific ROS scavenger N -tert-butyl-α-phenylnitrone (PBN), and superoxide specific scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL). These molecules resulted in reduced oxidative stress and changes in dopamine signaling [ 17 , 18 , 19 ]. Most importantly, these studies show that substances with antioxidant properties change not only cellular, but also behavioral phenotypes and can thus be useful in treating symptoms of substance abuse.…”

Section: Introductionmentioning

confidence: 99%

Influence of Redox and Dopamine Regulation in Cocaine-Induced Phenotypes Using Drosophila

et al. 2023

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Reactive Oxidative Species (ROS) are produced during cellular metabolism and their amount is finely regulated because of negative consequences that ROS accumulation has on cellular functioning and survival. However, ROS play an important role in maintaining a healthy brain by participating in cellular signaling and regulating neuronal plasticity, which led to a shift in our understanding of ROS from being solely detrimental to having a more complex role in the brain. Here we use Drosophila melanogaster to investigate the influence of ROS on behavioral phenotypes induced by single or double exposure to volatilized cocaine (vCOC), sensitivity and locomotor sensitization (LS). Sensitivity and LS depend on glutathione antioxidant defense. Catalase activity and hydrogen peroxide (H2O2) accumulation play a minor role, but their presence is necessary in dopaminergic and serotonergic neurons for LS. Feeding flies the antioxidant quercetin completely abolishes LS confirming the permissive role of H2O2 in the development of LS. This can only partially be rescued by co-feeding H2O2 or the dopamine precursor 3,4-dihydroxy-L-phenylalanine (L-DA) showing coordinate and similar contribution of dopamine and H2O2. Genetic versatility of Drosophila can be used as a tool for more precise dissection of temporal, spatial and transcriptional events that regulate behaviors induced by vCOC.

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Reactive oxygen species modulate locomotor activity and dopamine extracellular levels induced by amphetamine in rats

Cited by 3 publications

References 20 publications

Antioxidant Behavioural Phenotype in the Immp2l Gene Knock-Out Mouse

Antioxidant Behavioural Phenotype in the Immp2l Gene Knock-Out Mouse

Type 1 Corticotropin-Releasing Factor Receptor Differentially Modulates Neurotransmitter Levels in the Nucleus Accumbens of Juvenile versus Adult Rats

Influence of Redox and Dopamine Regulation in Cocaine-Induced Phenotypes Using Drosophila

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