Biology subjects

Ribeiro, D. E.

Publications and source records attributed to Ribeiro, D. E..

3 recordsLinked to original sources

bioRxiv2019

Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings

Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, presents rapid and sustained antidepressant effect in clinical and preclinical studies. Regarding ketamine effects on anxiety, there is a widespread discordance among pre-clinical studies. To address this issue, the present study reviewed the literature (electronic database MEDLINE) to summarize the profile of ketamine effects in animal tests of anxiety/fear. We found that ketamine anxiety/fear-related effects may depend on the anxiety paradigm, schedule of ketamine administration and tested species. Moreover, there was no report of ketamine effects in animal tests of fear related to panic disorder (PD). Based on that finding, we evaluated if treatment with ketamine and another NMDA antagonist, MK-801, would induce acute and sustained (24 hours later) anxiolytic and/or panicolytic-like effects in animals exposed to the elevated T-maze (ETM). The ETM evaluates, in the same animal, conflict-evoked and fear behaviors, which are related, respectively, to generalized anxiety disorder and PD. Male Wistar rats were systemically treated with racemic ketamine (10, 30 and 80 mg/kg) or MK-801 (0.05 and 0.1 mg/kg) and tested in the ETM in the same day or 24 hours after their administration. Ketamine did not affect the behavioral tasks performed in the ETM acutely or 24 h later. MK-801 impaired inhibitory avoidance in the ETM only at 45 min post-injection, suggesting a rapid but not sustained anxiolytic-like effect. Altogether our results suggest that ketamine might have mixed effects in anxiety tests while it does not affect panic-related behaviors.\n\nHighlightsO_LIKetamine induces mixed effects in animal anxiety tests\nC_LIO_LIFew studies investigated the individual effects of S-ketamine in anxiety/fear tests\nC_LIO_LINone study evaluated the effects of R-Ketamine on anxiety/fear-related behaviors\nC_LIO_LISystemic ketamine does not affect panic-like behaviors in the elevated T-maze\nC_LI

animal behavior and cognition↗

bioRxiv2018

Elevated P2x7r and P2x4r transcripts levels in the Flinders Sensitive Line Rats, a genetic animal model of depression

P2x7 and P2x4 receptors (P2x7R and P2x4R, respectively) are ligand-gated ion channels activated by adenosine triphosphate (ATP), which have been associated to dysfunctional processes in stress responses linked to depression, such as neurotransmitter release, cognition, sleep, energy, appetite, immune and endocrine dysfunction. Clinical studies indicate that polymorphisms in the P2x7r gene results in increased susceptibility for development of depression. Existing studies have investigated the role of P2x7R and P2x4R in animal models based on stress exposure. Therefore, the present work aimed to investigate the transcript and protein levels of these receptors in a genetic animal model of depression, the Flinders Sensitive Line (FSL) and its control group, the Flinders Resistant Line (FRL) rats. We found that FSL rats have increased transcript levels of P2x7R and P2x4R in frontal cortex (FC), ventral and dorsal hippocampus (vHip and dHip, respectively) compared to FRL rats. There were no alterations in the protein levels in the FC and dHip, but the P2x7R was lower in FSL than in FRL rats in the vHip. The results suggest that increased transcripts levels of P2x7r and P2x4r in the FSL rats may contribute to the stress-susceptibility observed in these animals.

neuroscience↗

bioRxiv2018

Activation of the TRKB receptor mediates the panicolytic-like effect of NOS inhibitor aminoguanidine

Nitric oxide (NO) triggers escape reactions in the dorsal periaqueductal gray matter (dPAG), a core structure mediating panic-associated responses, and decreases the release of BDNF in vitro. BDNF mediates the panicolytic effect induced by antidepressant drugs and produces these effects per se when injected into the dPAG. Based on these findings, we hypothesize that nitric oxide synthase (NOS) inhibitors would have panicolytic properties associated with increased BDNF signaling in the dPAG. We observed that the repeated (7 days), but not acute (1day), systemic administration of the NOS inhibitor aminoguanidine (AMG; 15 mg/kg/day) increased the latency to escape from the open arm of the elevated T-maze (ETM) and inhibited the number of jumps in hypoxia-induced escape reaction in rats, suggesting a panicolytic-like effect. Repeated, but not acute, AMG administration (15mg/kg) also decreased nitrite levels and increased TRKB phosphorylation at residues Y706/7 in the dPAG. Notwithstanding the lack of AMG effect on total BDNF levels in that structure, the microinjection of the TRK antagonist K252a into the dPAG blocked the anti-escape effect of this drug in the ETM. Taken together our data suggest that the inhibition of NO production by AMG increased the levels of pTRKB, which is required for the panicolytic-like effect observed.

neuroscience↗