Serotonin1A receptors in the dorsal hippocampus regulate working memory and long-term habituation in the hemiparkinsonian rats.

Abstract

Although the dorsal hippocampus (dHPC) and serotonin1A (5-HT1A) receptor are involved in cognition, their roles in cognitive impairments in Parkinson' disease (PD) are still unclear. In the present study, the effects of the 5-HT1A receptor agonist 8-OH-DPAT and antagonist WAY100635 administrated into the dHPC of rats were assessed in T-maze rewarded alternation test for working memory and in hole-board test for long-term habituation. Unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats impaired working memory and long-term habituation, decreased dopamine (DA) levels in the medial prefrontal cortex (mPFC), dHPC and ventral hippocampus (vHPC), and decreased the mean density of 5-HT1A receptors and co-localization of 5-HT1A receptor and excitatory amino acid carrier 1-immunoreactive (EAAC1-ir) neurons in the dHPC compared to sham-operated rats. Activation of dHPC 5-HT1A receptors by local infusion of 8-OH-DPAT impaired working memory and long-term habituation in both sham-operated and the 6-OHDA-lesioned rats. Furthermore, blockade of dHPC 5-HT1A receptors by WAY100635 improved the memories in the 6-OHDA-lesioned rats, but had no effects in sham-operated rats. Additionally, dHPC injection of 8-OH-DPAT decreased noradrenaline (NA) levels, increased 5-HT levels in the mPFC, dHPC and vHPC in sham-operated and lesioned rats, while WAY100635 increased DA and NA levels only in lesioned rats. The results of the present study suggest that dHPC 5-HT1A receptors regulate cognitive impairments in PD by changes of monoamines in the related brain regions.

• Authors: Ye Liu, Jian Liu, Si Rui Jiao, Xin Liu, Yuan Guo, Jin Zhang, Jie Yang, Wen Xie, Hui Sheng Wang, Li Zhang
• Journal: Behavioural brain research (Behav Brain Res) Vol. 376 Pg. 112207 (12 30 2019) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 31476331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Piperazines
• Pyridines
• Serotonin Receptor Agonists
• Receptor, Serotonin, 5-HT1A
• Serotonin
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Dopamine

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (pharmacology)
• Animals
• Disease Models, Animal
• Dopamine (metabolism)
• Habituation, Psychophysiologic (physiology)
• Hippocampus (metabolism, physiology)
• Male
• Medial Forebrain Bundle (drug effects)
• Memory (physiology)
• Memory, Short-Term (physiology)
• Neurons (metabolism)
• Parkinson Disease (metabolism, physiopathology)
• Parkinsonian Disorders (metabolism, physiopathology)
• Piperazines (pharmacology)
• Prefrontal Cortex (drug effects)
• Pyridines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Serotonin, 5-HT1A (metabolism, physiology)
• Serotonin (metabolism)
• Serotonin Receptor Agonists (pharmacology)
• Temporal Lobe (metabolism)