Arsenic decreases antinociceptive activity of paracetamol: Possible involvement of serotonergic and endocannabinoid receptors
Loading...
Date
2014
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
We assessed whether repeated arsenic exposure can decrease paracetamol-mediated antinociception by modulating serotonergic and endocannabinoid pathways. Rats were preexposed to elemental arsenic (4 ppm) as sodium arsenite through drinking water for 28 days. Next day paracetamol’s (400 mg/kg, oral) antinociceptive activity was assessed through formalin-induced nociception. Serotonin content and gene expression of 5-HT1A, 5-HT2A and CB1 receptors were evaluated in brainstem and frontal cortex. Arsenic decreased paracetamol-mediated analgesia. Paracetamol, but not arsenic, increased serotonin content in these regions. Arsenic attenuated paracetamol-mediated increase in serotonin level. Paracetamol did not alter 5-HT1Aexpression, but caused down-regulation of 5-HT2Aand up-regulation of CB1 receptors. Arsenic down-regulated these receptors. However,paracetamol-mediated down-regulation of 5-HT2Awas more pronounced. Arsenic did not modify paracetamol’s effect on 5-HT1A expression, but reduced paracetamol - mediated down - regulation of 5-HT2A and reversed up-regulation of CB1 receptors. Results suggest arsenic reduced paracetamol-induced analgesia possibly by interfering with pronociceptive 5-HT2A and antinociceptive CB1 receptors.
Description
TNV_ETP_2014_38(397-405)
Keywords
Veterinary Science