Cheng Xue Du1, Yuan Guo1, Qiao Jun Zhang2, Jin Zhang1, Shu Xuan Lv1, Jian Liu1,3. 1. a Department of Physiology and Pathophysiology, School of Basic Medical Sciences , Xi'an Jiaotong University Health Science Center , Xi'an , China. 2. b Department of Rehabilitation Medicine , The Second Hospital, Xi'an Jiaotong University , Xi'an , China. 3. c Key Laboratory of Environment and Genes Related to Diseases , Ministry of Education of China , Xi'an , China.
Abstract
OBJECTIVE: At present, little is known about the role of serotonin7 (5-HT7) receptor in anxiety, particularly in Parkinson's disease-related anxiety. Here, we tested whether 5-HT7 receptors in the prelimbic (PrL) cortex are involved in the regulation of anxiety-like behaviors in sham-operated rats and rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle (MFB). METHODS: The open field and elevated plus maze (EPM) tests were performed to study the influence of MFB lesion and intra-PrL injection of 5-HT7 agonist AS19 (0.5, 1 or 2 μg/rat) and antagonist SB269970 (1.5, 3 or 6 μg/rat) on anxiety-like behaviors. Additionally, changes in monoamine levels in limbic and limbic-related brain regions were observed after intra-PrL injection of AS19 (2 μg/rat) and SB269970 (6 μg/rat). RESULTS: The MFB lesion induced anxiety-like behaviors compared to sham-operated rats. Intra-PrL injection of AS19 showed anxiolytic effects by the open field and EPM tests in two groups of rats, and administration of SB269970 showed anxiogenic responses. However, the doses producing these effects in the lesioned rats were higher than those in sham-operated rats. Neurochemical results showed that intra-PrL injection of AS19 increased dopamine, 5-HT and noradrenaline (NA) levels in the medial prefrontal cortex, ventral hippocampus and amygdala in two groups of rats, whereas SB269970 decreased 5-HT and NA levels in these brain regions. DISCUSSION: 5-HT7 receptors in the PrL are involved in the regulation of anxiety-like behaviors, which is attributable to changes in dopamine, 5-HT and NA levels in the limbic and limbic-related brain regions after activation and blockade of 5-HT7 receptors. ABBREVIATIONS: 6-OHDA: 6-hydroxydopamine; DMSO: dimethyl sulfoxide; DA: dopamine; EPM: elevated plus maze; MFB: medial forebrain bundlem; PFC: medial prefrontal cortex; NA: noradrenaline; PD: Pakinson's disease; PrL: prelimbic; 5-HT: serotonin; vHip: ventral hippocampus.
OBJECTIVE: At present, little is known about the role of serotonin7 (5-HT7) receptor in anxiety, particularly in Parkinson's disease-related anxiety. Here, we tested whether 5-HT7 receptors in the prelimbic (PrL) cortex are involved in the regulation of anxiety-like behaviors in sham-operated rats and rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle (MFB). METHODS: The open field and elevated plus maze (EPM) tests were performed to study the influence of MFB lesion and intra-PrL injection of 5-HT7 agonist AS19 (0.5, 1 or 2 μg/rat) and antagonist SB269970 (1.5, 3 or 6 μg/rat) on anxiety-like behaviors. Additionally, changes in monoamine levels in limbic and limbic-related brain regions were observed after intra-PrL injection of AS19 (2 μg/rat) and SB269970 (6 μg/rat). RESULTS: The MFB lesion induced anxiety-like behaviors compared to sham-operated rats. Intra-PrL injection of AS19 showed anxiolytic effects by the open field and EPM tests in two groups of rats, and administration of SB269970 showed anxiogenic responses. However, the doses producing these effects in the lesioned rats were higher than those in sham-operated rats. Neurochemical results showed that intra-PrL injection of AS19 increased dopamine, 5-HT and noradrenaline (NA) levels in the medial prefrontal cortex, ventral hippocampus and amygdala in two groups of rats, whereas SB269970 decreased 5-HT and NA levels in these brain regions. DISCUSSION: 5-HT7 receptors in the PrL are involved in the regulation of anxiety-like behaviors, which is attributable to changes in dopamine, 5-HT and NA levels in the limbic and limbic-related brain regions after activation and blockade of 5-HT7 receptors. ABBREVIATIONS: 6-OHDA: 6-hydroxydopamine; DMSO: dimethyl sulfoxide; DA: dopamine; EPM: elevated plus maze; MFB: medial forebrain bundlem; PFC: medial prefrontal cortex; NA: noradrenaline; PD: Pakinson's disease; PrL: prelimbic; 5-HT: serotonin; vHip: ventral hippocampus.
Authors: Gregory M Pontone; Nadeeka Dissanayka; Liana Apostolova; Richard G Brown; Roseanne Dobkin; Kathy Dujardin; Joseph H Friedman; Albert F G Leentjens; Eric J Lenze; Laura Marsh; Lynda Mari; Oury Monchi; Irene H Richard; Anette Schrag; Antonio P Strafella; Beth Vernaleo; Daniel Weintraub; Zoltan Mari Journal: NPJ Parkinsons Dis Date: 2019-12-11