Microdialysis in vivo Evaluation of the effects of SA-4503, a Sigma1 Receptor Agonist, on the Levels of Monoamines in the Prefrontal Cortex of Conscious Rats

Francesco Crespi

doi:10.31579/2578-8868/164

Abstract

Sigma receptors are widespread in the central nervous system and are differentiated in two subtypes, sigma1 and sigma2. In particular, the sigma1 receptor subtype appears to be able to influence biological mechanisms connected with neuro-degeneration. Furthermore, several studies are implicating sigma1 receptor agonists within antidepressant activity. Evidence of prefrontal cortex abnormalities in clinically depressed subjects have been reported by several works and that monoamines such as serotonin and cathecolamines can be involved in such malfunctions. Up to now the most of the preclinical work performed to analyze the influence of sigma1 receptor agonists upon catecholaminergic and serotoninergic activities in brain areas has been done by means of in vitro as well as ex vivo methodologies. Here, SA-4503, a selective sigma1 receptor agonist with potential antidepressant activity has been tested in vivo upon dopamine (DA), noradrenaline (NA) and serotonin (5-HT) levels detected by micro-dialysis in the medial Prefrontal Cortex (mPFC) of freely moving rats.

Highlights

Sigma receptors are widespread in the central nervous system and across multiple peripheral tissues
The effects of SA-4503, a selective sigma1 receptor agonist with potential antidepressant activity [24, 25] has been tested in vivo upon dopamine (DA), noradrenaline (NA) and serotonin (5-HT) levels in the medial Prefrontal Cortex of freely moving rats prepared for micro-dialysis as described earlier [26, 27, 28]
The in vivo data collected in the medial Prefrontal Cortex (mPFC) following the treatment with SA4503 showed that:

Summary

Introduction

Sigma receptors are widespread in the central nervous system and across multiple peripheral tissues. Sigma receptors were initially described in 1976 as opiate receptors. They were successively differentiated in two subtypes, sigma and sigma2 [1, 2]. More recently it has been shown that these receptors are non-opioid, are trans-membrane proteins and play various purposes in intracellular signaling, apoptosis and metabolic regulation It has been shown that sigma receptors and in particular the sigma receptor subtype is expressed in both neuronal as well as cerebral glia cells and appear to be able to influence biological mechanisms connected with neuro-degeneration [4] sigma receptors may be considered as targets for the development of pharmacological approaches to treat various CNS disorders It has been shown that sigma receptors and in particular the sigma receptor subtype is expressed in both neuronal as well as cerebral glia cells and appear to be able to influence biological mechanisms connected with neuro-degeneration [4] sigma receptors may be considered as targets for the development of pharmacological approaches to treat various CNS disorders (for a review see ref. 5)

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Conclusion