We assessed whether repeated arsenic exposure can decrease paracetamol-mediated antinociception by modulating serotonergic and endocannabinoid pathways. Rats were preexposed to elemental arsenic (4ppm) as sodium arsenite through drinking water for 28 days. Next day paracetamol's (400mg/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-HT1A expression, but caused down-regulation of 5-HT2A and up-regulation of CB1 receptors. Arsenic down-regulated these receptors. However, paracetamol-mediated down-regulation of 5-HT2A was 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.
Keywords: 5-HT receptors, CB(1) receptor; Antinociception; Arsenic; Paracetamol; Rat.
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