The Effects of N-Acetylcysteine on the Rat Mesocorticolimbic Pathway: Role of mGluR5 Receptors and Interaction with Ethanol

Abstract

N-acetylcysteine (NAC) is a prodrug that is marketed as a mucolytic agent and used for the treatment of acetaminophen overdose. Over the last few decades, evidence has been gathered that suggests the potential use of NAC as a new pharmacotherapy for alcohol use disorder (AUD), although its mechanism of action is already being debated. In this paper, we set out to assess both the potential involvement of the glutamate metabotropic receptors (mGluR) in the possible dual effect of NAC administered at two different doses and NAC’s effect on ethanol-induced activation. To this aim, 30 or 120 mg/kg of NAC was intraperitoneally administered to rats with the presence or absence of the negative allosteric modulator of mGluR5 (MTEP 0.1 mg/kg). Thereafter, the cFOS IR-cell expression was analyzed. Secondly, we explored the effect of 120 mg/kg of NAC on the neurochemical and behavioral activation induced by intra-VTA ethanol administration (150 nmol). Our results showed that the high NAC dose stimulated cFOS expression in the NAcc, and that this effect was suppressed in the presence of MTEP, thus suggesting the implication of mGluR5. Additionally, high doses could attenuate the ethanol-induced increase in cFOS-expression in the NAcc, probably due to a phenomenon based on the long-term depression of the MSNs. Additional experiments are required to corroborate our hypothesis.

Probiotics alleviate depression-like behavior in mother-infant separation stress rats

“…Probiotics are a simple and readily available complementary intervention that is involved in the development, growth and maturation of multiple systems, and many diseases have been shown to havea strong association with probiotics, For example, irritable bowel syndrome [41] 、Metabolic syndrome [42] 、Allergic diseases [43] etc, And probiotics have a positive effect on neurological development, cognitivefunction, behavior and emotional regulation [44] . A growing number of studies have shown that for infants and young children experiencing early life stressful events, the addition of probiotics from breast milk to formula mimics to some extent the nutritional supply of breast milk to infants and young children to achieve healthy growth [45,46] .…”