5-HT6 receptor agonist and antagonist modulates ICV-STZ-induced memory impairment in rats.
Psychopharmacology (Berl)
; 235(5): 1557-1570, 2018 05.
Article
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| MEDLINE
| ID: mdl-29502275
ABSTRACT
RATIONALE AND OBJECTIVES:
5-HT6 receptors are mainly expressed in brain areas associated with learning and memory. Several studies have reported procognitive effects of both 5-HT6 agonist and antagonists. However, the exact mechanism 5-HT6 receptor modulation has not been properly studied especially in the context of cholinergic functions, cerebral blood flow (CBF), brain-derived neural factor (BDNF), oxidative stress, and behavioral changes.METHODS:
In the present study, memory impairment was induced in albino Wistar rats by two doses of intracerebroventricular (ICV) injection of streptozotocin (STZ, 3 mg/kg) on first and third day. These rats were evaluated in a battery of behavioral tasks after 14 days from the first day of ICV-STZ.RESULTS:
Significant memory impairment was seen when ICV-STZ induced rats are assessed by Morris water maze, novel object recognition, social recognition, and passive avoidance tests. There was a significant reduction in CBF, increased oxidative stress (MDA, GSH, and ROS), acetylcholinesterase (AChE) activity, and a decrease in BDNF. Treatment with selective 5-HT6 agonist EMD-386088 (5 mg/kg) and antagonist SB-399885 (10 mg/kg) prevented ICV-STZ-induced memory impairment when assessed by behavioral tests. Treatment with 5-HT6 ligands significantly prevented the change in CBF and BDNF. Further, protected from MDA and ROS and decreasing GSH in the brain compared to ICV-STZ rats. The rice in brain AChE activity was normalized by both ligands. The changes in locomotor activity by EMD-386088 and SB-399885 treatment were negligible.CONCLUSION:
The findings in this study support the therapeutic potential of 5-HT6 receptor ligands in the treatment of cognitive dysfunction.Palabras clave
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Banco de datos:
MEDLINE
Asunto principal:
Antagonistas de la Serotonina
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Receptores de Serotonina
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Agonistas de Receptores de Serotonina
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Estreptozocina
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Trastornos de la Memoria
Límite:
Animals
Idioma:
En
Año:
2018
Tipo del documento:
Article