title: Decreased response of interneurons in the medial prefrontal cortex to 5-HT₁A receptor activation in the rat 6-hydroxydopamine Parkinson model.
abstract: This study examined the response of interneurons in the medial prefrontal cortex (mPFC) to 5-HT1A receptor agonist 8-OH-DPAT and change in expression of 5-HT1A receptor on glutamate decarboxylase 67 (GAD67)-positive neurons in rats with 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc). Systemic administration of 5-HT1A receptor agonist 8-OH-DPAT dose-dependently inhibited the firing rate of the interneurons at all doses tested in sham-operated rats. In 6-OHDA-lesioned rats, 8-OH-DPAT, at the same doses, also inhibited the firing rate of the interneurons, whereas the inhibition was significant only at a high cumulative dose. Furthermore, injection of 8-OH-DPAT into the mPFC inhibited the interneurons in sham-operated rats, while having no effect on firing rate of the interneurons in 6-OHDA-lesioned rats. In contrast to sham-operated rats, SNc lesion reduced the expression of 5-HT1A receptor on GAD67-positive neurons in the prelimbic cortex, a sub-region of the mPFC. Our results indicate that degeneration of the nigrostriatal pathway leads to decreased response of mPFC interneurons to 5-HT1A receptor activation, which attributes to the down-regulation of 5-HT1A receptor expression in these interneurons.
authors.affiliation: Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi Wu Lu 157, Xi'an, 710004, China, zhangqj@mail.xjtu.edu.cn.
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.forename: Hongfei
authors.initials: H
authors.lastname: Qiao
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Niu
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005968:Glutamate Decarboxylase / Q000032:analysis; D007395:Interneurons / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008297:Male; D009410:Nerve Degeneration; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1