5-HT6 receptor agonist and antagonist modulates ICV-STZ-induced memory impairment in rats

Anand M. Bokare, Mandar Bhonde, Rajan Goel, Yogendra Nayak

Research output: Contribution to journalArticle

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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.

LanguageEnglish
Pages1557-1570
Number of pages14
JournalPsychopharmacology
Volume235
Issue number5
DOIs
Publication statusPublished - 01-05-2018

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Cerebrovascular Circulation
Brain
Acetylcholinesterase
Ligands
Oxidative Stress
Therapeutics
Locomotion
Streptozocin
Cholinergic Agents
serotonin 6 receptor
Wistar Rats
Learning
Injections
Water
5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole
SB 399885
Recognition (Psychology)

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Bokare, Anand M. ; Bhonde, Mandar ; Goel, Rajan ; Nayak, Yogendra. / 5-HT6 receptor agonist and antagonist modulates ICV-STZ-induced memory impairment in rats. In: Psychopharmacology. 2018 ; Vol. 235, No. 5. pp. 1557-1570.
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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.",
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5-HT6 receptor agonist and antagonist modulates ICV-STZ-induced memory impairment in rats. / Bokare, Anand M.; Bhonde, Mandar; Goel, Rajan; Nayak, Yogendra.

In: Psychopharmacology, Vol. 235, No. 5, 01.05.2018, p. 1557-1570.

Research output: Contribution to journalArticle

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T1 - 5-HT6 receptor agonist and antagonist modulates ICV-STZ-induced memory impairment in rats

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AU - Bhonde, Mandar

AU - Goel, Rajan

AU - Nayak, Yogendra

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