title: Arsenic decreases antinociceptive activity of paracetamol: possible involvement of serotonergic and endocannabinoid receptors.
abstract: 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.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Karunakaran
authors.initials: K
authors.lastname: Vijayakaran
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Manickam
authors.initials: M
authors.lastname: Kesavan
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Kandasamy
authors.initials: K
authors.lastname: Kannan
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Palanisamy
authors.initials: P
authors.lastname: Sankar
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India.
authors.forename: Surendra Kumar
authors.initials: SK
authors.lastname: Tandan
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh, India. Electronic address: snsarkar1911@gmail.com.
authors.forename: Souvendra Nath
authors.initials: SN
authors.lastname: Sarkar
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001933:Brain Stem / Q000378:metabolism; D060766:Drinking Water / Q000737:chemistry*; D004347:Drug Interactions; D005625:Frontal Lobe / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D017670:Sodium Compounds / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000700:Analgesics; D018053:Arsenites; D060766:Drinking Water; D043884:Receptor, Cannabinoid, CB1; D011985:Receptors, Serotonin; D017670:Sodium Compounds; D014874:Water Pollutants, Chemical; D000082:Acetaminophen; C017947:sodium arsenite
keywords: 5-HT receptors, CB(1) receptor; Antinociception; Arsenic; Paracetamol; Rat