Toxic effects of methoxychlor in rat striatum: modifications in several neurotransmitters

Abstract

Neurotoxic effects of methoxychlor (MTX) are poorly understood at present. This study was undertaken to evaluate the possible effects of MTX in norepinephrine, dopamine and amino acid contents and serotonin turnover in rat striatum. For this purpose, adult male Sprague-Dawley rats were administered 25 mg/kg/day of MTX in sesame oil or vehicle only for 30 days. The neurotransmitters of interest were measured in the striatum by HPLC. MTX decreased norepinephrine and 5-hydroxyindole acetic acid (5-HIAA) content and serotonin turnover (measured as 5-HIAA/serotonin ratio), and increased glutamate and GABA concentrations. However, the content of serotonin, aspartate, glutamine and taurine was not modified by MTX exposure. These data suggest that MTX exposure inhibits norepinephrine synthesis and serotonin metabolism. The inhibitory effect on norepinephrine could be explained, at least in part, by the increase of both GABA and glutamate contents. Further studies are needed to understand the effects of MTX on serotonin. Also a disruptive effect of MTX on the metabolisms of glutamate, aspartate, glutamine and GABA emerges.

The Dynamics of Autism Spectrum Disorders: How Neurotoxic Compounds and Neurotransmitters Interact

“…With respect to Glu, exposure to 25 mg/kg of methoxychlor for 30 days increased striatal Glu levels in adult male Sprague-Dawley rats [67]. The findings of Cabaleiro et al .…”

“…However, exposure to methoxychlor reduced 5-HT levels in the posterior hypothalamus ( p ≤ 0.05). No effects on 5-HT were found in a second study by the same authors, investigating effects of methoxychlor exposure in the striatum, using the same population, dose, length of exposure and analysis techniques [67]. …”

Initial study on the possible mechanisms involved in the effects of high doses of perfluorooctane sulfonate (PFOS) on prolactin secretion

“…GABA concentration was determined in the anterior and in the mediobasal hypothalamus by HPLC with fluorescence detection after precolumn derivatization reaction with O-phthalaldehyde (OPA) (Lafuente et al, 2007). A C-18 reverse-column filled with nucleosil (with a pore diameter of 5 mm, an internal diameter of 4.6 nm and a length of 150 mm (Phoenomenex)) was used for separation.…”

Cadmium chloride exposure modifies amino acid daily pattern in the mediobasal hypothalamus in adult male rat

“…At the end of the treatment, groups of 10 animals were killed by decapitation at six diff erent time intervals around the clock, beginning at 08:00 h. Samples were taken every 4 h. Care was taken to avoid any major stress to the animals before sacrifi ce, and the decapitation procedure was completed within 5-7 s. The mediobasal hypothalamus was immediately removed and homogenized in cold 2 M acetic acid (1-4 °C), processed as previously described (Lafuente et al, 2007) and kept frozen at −80 °C until aspartate, glutamate, glutamine, GABA and taurine determinations. In each sample, protein content was determined by the Bradford method (Bradford, 1976).…”

“…Aspartate, glutamate, glutamine, GABA and taurine were separated and analyzed using high-performance liquid chromatography (HPLC), with fl uorescence detection after precolumn derivatization with o-phtalaldehyde (OPA), as previously described (Lafuente et al, 2005b(Lafuente et al, , 2007. An aliquot of 20 μl of the tissue supernatant containing homoserine as internal standard was neutralized with OPA reagent (4 mM OPA, 10% methanol, 2.56 mM 2-mercaptoethanol, in 1.6 M potassium borate buff er, pH 9.5) for 1 min.…”