title: Multi-system state shifts and cognitive deficits induced by chronic morphine during abstinence.
abstract: Chronic morphine administration induces neural plasticity followed by withdraw. And clinic observation indicates that obvious cognitive deficits are found during withdrawal. However, current neural substrates that regulate dysfunction in withdrawal are unknown. In our studies, chronic morphine administration was used to induce the spontaneous withdrawal model in rats. A series of cognitive abilities was tested to explore brain function. To further evaluate the neural substrates of dysfunction, Manganese-enhanced MRI(MEMRI) was used to map the dysfunctional regions in vivo.We observed that chronic morphine administration could induce obvious withdrawal behaviors in abstinence followed by cognitive impairments, such as impairments in working memory, reward, interaction and enhancement of anxiety. Our in-vivo MEMRI data using the voxel-wise comparisons showed that the manganese-enhanced signal intensity (VMI) within morphine withdrawal groups was increased in cingulate cortex (Cg), secondary motor cortex (M2), CA3 subfield of hippocampus, dorsal striatum (D-striatum), retrosplenial cortex (RS), shell subregion of NAc (AcbSh), core subregion of NAc (AcbC), central nucleus of amygdala (CeC), basolateral amygdaloid nucleus (BLA), central amygdaloid nucleus (CeM), anterior hypothalamic area, central (AHC), ventral tegmental area (VTA) and scaphoid thalamic nucleus (SC).However, decreasing of VMI was found in the ventrolateral striatum (V-striatum) and lateral posterior thalamic nucleus (LP) compared to the control group. These brain regions were beleived to be components of the memory, executive, limbic and regulatory systems. Therefore, our present studies indicate that withdrawal induced by chronic morphine adiministration could disturb brain function leading to multi-systems state shifts and cognitive deficits in abstinence.
authors.affiliation: Department of Genetics, Xuzhou Medical University, Xuzhou, China.
authors.forename: Haichen
authors.initials: H
authors.lastname: Niu
authors.affiliation: Affiliated Xuzhou Hospital of Medical college, Southeast University, Xuzhou, China.
authors.forename: Guanqun
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Genetics, Xuzhou Medical University, Xuzhou, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Genetics, Xuzhou Medical University, Xuzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Health Statistics, Xuzhou Medical University, Xuzhou, China.
authors.forename: Tongzhou
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Health Statistics, Xuzhou Medical University, Xuzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
authors.affiliation: Research Facility Center for Morphology, Xuzhou Medical University, Xuzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Genetics, Xuzhou Medical University, Xuzhou, China.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Audiology and Speech Science, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. Electronic address: oto8558@163.com.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Department of Ophthalmology, Second People's Hospital of Yunnan Province, Kunming, China. Electronic address: fudanhumin@sina.com.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D001931:Brain Mapping; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology / Q000523:psychology*; D004644:Emotions; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D009020:Morphine / Q000009:adverse effects*; D017207:Rats, Sprague-Dawley; D012201:Reward; D012919:Social Behavior; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000503:physiopathology / Q000523:psychology*
chemical_list: D000697:Central Nervous System Stimulants; D009020:Morphine
keywords: Cognitive; Manganese-enhanced MRI; Morphine; Withdrawal