title: Activation of serotonin2A receptors in the medial septum-diagonal band of Broca complex enhanced working memory in the hemiparkinsonian rats.
abstract: Serotonin2A (5-HT2A) receptors are highly expressed in the medial septum-diagonal band of Broca complex (MS-DB), especially in parvalbumin (PV)-positive neurons linked to hippocampal theta rhythm, which is involved in cognition. Cognitive impairments commonly occur in Parkinson's disease. Here we performed behavioral, electrophysiological, neurochemical and immunohistochemical studies in rats with complete unilateral 6-hydroxydopamine lesions of the medial forebrain bundle (MFB) to assess the importance of dopamine (DA) depletion and MS-DB 5-HT2A receptors for working memory. The MFB lesions resulted in working memory impairment and decreases in firing rate and density of MS-DB PV-positive neurons, peak frequency of hippocampal theta rhythm, and DA levels in septohippocampal system and medial prefrontal cortex (mPFC) compared to control rats. Intra-MS-DB injection of high affinity 5-HT2A receptor agonist TCB-2 enhanced working memory, increased firing rate of PV-positive neurons and peak frequency of hippocampal theta rhythm, elevated DA levels in the hippocampus and mPFC, and decreased 5-HT level in the hippocampus in control and lesioned rats. Compared to control rats, the duration of the excitatory effect produced by TCB-2 on the firing rate of PV-positive neurons was markedly shortened in lesioned rats, indicating dysfunction of 5-HT2A receptors. These findings suggest that unilateral lesions of the MFB in rats induced working memory deficit, and activation of MS-DB 5-HT2A receptors enhanced working memory, which may be due to changes in the activity of septohippocampal network and monoamine levels in the hippocampus and mPFC.
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Yi-Na
authors.initials: YN
authors.lastname: Sun
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Ling-Na
authors.initials: LN
authors.lastname: Han
authors.affiliation: Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: Zhong-Heng
authors.initials: ZH
authors.lastname: Wu
authors.affiliation: Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: Qiao-Jun
authors.initials: QJ
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: liujian@mail.xjtu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000032:analysis; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D020667:Diagonal Band of Broca / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology*; D008744:Methylamines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D020734:Parkinsonian Disorders / Q000503:physiopathology* / Q000523:psychology*; D010320:Parvalbumins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D012686:Septal Nuclei / Q000187:drug effects / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D013826:Theta Rhythm / Q000187:drug effects
chemical_list: C514172:(4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine; D015306:Biogenic Monoamines; D001643:Bridged Bicyclo Compounds; D008744:Methylamines; D010320:Parvalbumins; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists
keywords: 5-HT(2A) receptors; Medial septum-diagonal band of Broca complex; Parkinson's disease; Parvalbumin; Working memory