TY - JOUR
T1 - Agonist E-6837 and antagonist SB-271046 of 5-HT 6 receptors both reverse the depressive-like effect induced in mice by subchronic ketamine administration
AU - Suárez-Santiago, José E.
AU - Briones-Aranda, Alfredo
AU - Espinosa-Raya, Judith
AU - Picazo, Ofir
N1 - Publisher Copyright:
© 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2017/7/12
Y1 - 2017/7/12
N2 - Major depression is one of the most common affective disorders caused by schizophrenia. The administration of N-methyl-d-Aspartate receptor antagonists, such as ketamine, can reproduce the negative and affective symptoms of this disorder in animals. Preclinical studies have shown that 5-HT 6 receptor (5-HT 6 R) agonists and antagonists have a considerable antipsychotic response. The aim of the present study was to evaluate the effect of an acute treatment with an agonist, E-6837, and an antagonist, SB-271046, of 5-HT 6 R on the immobility induced in mice by a subchronic ketamine regimen (5 days; 10 mg/kg/day, intraperitoneal). Repeated ketamine administration alone increased the immobility time in the forced-swimming test and the tail-suspension test. E-6837 at 10 and 20 mg/kg caused a significant reduction of immobility in the tail-suspension test and forced-swimming test, respectively. Interestingly, SB-271046 (10 mg/kg) also elicited an antidepressant-like effect in both tests. The current findings suggest an important role for these 5-HT 6 R ligands as mood modulators. However, it is necessary to explore the physiological mechanisms involved in this process in greater detail.
AB - Major depression is one of the most common affective disorders caused by schizophrenia. The administration of N-methyl-d-Aspartate receptor antagonists, such as ketamine, can reproduce the negative and affective symptoms of this disorder in animals. Preclinical studies have shown that 5-HT 6 receptor (5-HT 6 R) agonists and antagonists have a considerable antipsychotic response. The aim of the present study was to evaluate the effect of an acute treatment with an agonist, E-6837, and an antagonist, SB-271046, of 5-HT 6 R on the immobility induced in mice by a subchronic ketamine regimen (5 days; 10 mg/kg/day, intraperitoneal). Repeated ketamine administration alone increased the immobility time in the forced-swimming test and the tail-suspension test. E-6837 at 10 and 20 mg/kg caused a significant reduction of immobility in the tail-suspension test and forced-swimming test, respectively. Interestingly, SB-271046 (10 mg/kg) also elicited an antidepressant-like effect in both tests. The current findings suggest an important role for these 5-HT 6 R ligands as mood modulators. However, it is necessary to explore the physiological mechanisms involved in this process in greater detail.
KW - 5-HT 6 receptor
KW - E-6837
KW - SB-271046
KW - depression
KW - forced-swimming test
KW - ketamine
KW - mouse
KW - tail-suspension test
UR - http://www.scopus.com/inward/record.url?scp=85023776579&partnerID=8YFLogxK
U2 - 10.1097/FBP.0000000000000327
DO - 10.1097/FBP.0000000000000327
M3 - Artículo
C2 - 28704275
SN - 0955-8810
VL - 28
SP - 582
EP - 585
JO - Behavioural Pharmacology
JF - Behavioural Pharmacology
IS - 7
ER -