Activation of 5-HT2C (but not 5-H-1A) receptors in the amygdala enhances fear-induced antinociception: Blockade with local 5-H-2C antagonist or systemic fluoxetine

Author(s)

Rodrigues Tavares, Ligia Renata ^{[1, 2]} ; Baptista-de-Souza, Daniela ^{[2, 3]} ; Canto-de-Souza, Azair ^{[1, 2, 3, 4]}

Affiliation

^[1] UNESP, UFSCar, Joint Grad Program Physiol Sci, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Fed Sao Carlos, CECH, Dept Psychol, Psychobiol Grp, Rod Washington Luis, Km 235 Monjolinho, BR-13565905 Sao Carlos, SP - Brazil

^[3] Neurosci & Behav Inst IneC, BR-14040901 Ribeirao Preto, SP - Brazil

^[4] Univ Fed Sao Carlos, Psychol Program, BR-13565905 Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: Neuropharmacology; v. 135, p. 376-385, JUN 2018.
• Web of Science Citations: 2

Abstract

It is well-known that the exposure of rodents to threatening environments {[}e.g., the open arm of the elevated-plus maze (EPM)] elicits pain inhibition. Systemic and/or intracerebral {[}e.g., periaqueductal gray matter, amygdala) injections of antiaversive drugs {[}e.g., serotonin (5-HT) ligands, selective serotonin reuptake inhibitors (SSRIs)] have been used to change EPM-open arm confinement induced anti-nociception (OAA). Here, we investigated (i) the role of the 5-HT1A and 5-HT2C receptors located in the amygdaloid complex on OAA as well as (ii) the effects of systemic pretreatment with fluoxetine (an SSRI) on the effects of intra-amygdala injections of 8-OH-DPAT (a 5-HT1A agonist) or MK-212 (a 5-HT2C agonist) on nociception in mice confined to the open arm or enclosed arm of the EPM. Nociception was assessed by the writhing test. Intra-amygdala injections of 8-OH-DPAT (10 nmol) or MK-212 (0.63 nmol) produced a pronociceptive effect and intensified OAA, respectively. Fluoxetine (2.5 mg/kg, intraperitoneally) did not change 8-OH-DPAT effects on nociception but antagonized the enhancement of the OAA produced by MK-212. Interestingly, prior injection of SB 242084 (a selective 5-HT2C antagonist) into the amygdala also blocked the MK-212 effects on OAA. These results indicate that 5-HT may facilitate nociception and intensify OAA, respectively, at 5-HT1A and 5-HT2C receptors located in the amygdala of mice. The impairment produced by systemic fluoxetine on the OAA enhancement provoked by intra-amygdala MK-212 suggests that this type of fear-induced antinociception may be modulated by SSRIs. (C) 2018 Published by Elsevier Ltd. (AU)

• FAPESP's process: 09/17938-6 - Role of serotonergic receptors of periaqueductal gray on antinociception of mice confined to open arms the elevated plus-maze
• Grantee: Daniela Baptista de Souza
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)