Anxiogenic effect of median raphe nucleus lesion in stressed rats

Netto, Sueli Mendonça; Silveira, Ricardo dos Reis; Coimbra, Norberto Cysne; Joca, Sâmia Regiane Lourenço; Guimarães, Francisco Silveira

doi:10.1016/s0278-5846(02)00248-8

Cited by 48 publications

(21 citation statements)

References 32 publications

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“…This is in accordance with the chronic unpredicted mild stress rat model of depression, where intra-hippocampal infusion of 5-HT was sufficient to rescue reduced food intake, as well as impaired spontaneous behavior (Luo et al, 2008). Further, experimental 5-HT depletion was shown to associate with increased anxiety in response to novelty (Hohmann et al, 2007); although the impact on anxiety per se is yet not clear, potentially relating to stress as a contributing factor (Andrade and Graeff, 2001; Netto et al, 2002). Consistently, BAC alpha-synuclein rats displayed less visits of the center zone not as an immediate effect but rather a more rapid decline in activity, conveying the impression of less exploratory motivation in response to novelty.…”

Section: Discussionmentioning

confidence: 99%

Severely impaired hippocampal neurogenesis associates with an early serotonergic deficit in a BAC α-synuclein transgenic rat model of Parkinson's disease

Kohl

́Abdallah

Vogelgsang

et al. 2016

Neurobiology of Disease

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Parkinson's disease (PD) is a multisystem disorder, involving several monoaminergic neurotransmitter systems resulting in a broad range of motor and non-motor symptoms. Pathological hallmarks of PD are the loss of dopaminergic neurons and the accumulation of alpha-synuclein, however also being present in the serotonergic raphe nuclei early in the disease course. The dysfunction of the serotonergic system projecting to the hippocampus might contribute to early non-motor symptoms such as anxiety and depression. The adult hippocampal dentate gyrus (DG), a unique niche of the forebrain continuously generating new neurons, may particularly present enhanced susceptibility towards accumulating alpha-synuclein levels. The underlying molecular mechanisms in the context of neuronal maturation and survival of new-born neurons are yet not well understood. To characterize the effects of overexpression of human full-length alpha-synuclein on hippocampal cellular and synaptic plasticity, we used a recently generated BAC alpha-synuclein transgenic rat model showing important features of PD such as widespread and progressive alpha-synuclein aggregation pathology, dopamine loss and age-dependent motor decline. At the age of four months, thus prior to the occurrence of the motor phenotype, we observed a profoundly impaired dendritogenesis of neuroblasts in the hippocampal DG resulting in severely reduced survival of adult new-born neurons. Diminished neurogenesis concurred with a serotonergic deficit in the hippocampus as defined by reduced levels of serotonin (5-HT) 1B receptor, decreased 5-HT neurotransmitter levels, and a loss of serotonergic nerve terminals innervating the DG/CA3 subfield, while the number of serotonergic neurons in the raphe nuclei remained unchanged. Moreover, alpha-synuclein overexpression reduced proteins involved in vesicle release, in particular synapsin-1 and Rab3 interacting molecule (RIM3), in conjunction with an altered ultrastructural architecture of hippocampal synapses. Importantly, alterations of the hippocampal serotonergic system were associated with an anxiety-like behavior consisting of reduced exploratory behavior and feeding in transgenic rats. Taken together, these findings imply that accumulating alpha-synuclein severely affects hippocampal neurogenesis paralleled by impaired 5-HT neurotransmission prior to the onset of aggregation pathology and motor deficits in this transgenic rat model of PD.

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Section: Discussionmentioning

confidence: 99%

Severely impaired hippocampal neurogenesis associates with an early serotonergic deficit in a BAC α-synuclein transgenic rat model of Parkinson's disease

Kohl

́Abdallah

Vogelgsang

et al. 2016

Neurobiology of Disease

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“…Yet, findings from previous studies examining effects of repeated restraint on anxiety in the EPM are mixed, with increased [25,60] or unchanged anxiety levels [59,61,62] sometimes observed. Inconsistent results in the effects of repeated restraint stress on EPM anxiety levels may be related to methodological differences across laboratories, since the EPM has been shown to be sensitive to procedural differences, including different housing conditions [50,51] and handling procedures [47].…”

Section: Discussionmentioning

confidence: 99%

Social and non-social anxiety in adolescent and adult rats after repeated restraint

Doremus-Fitzwater¹,

Varlinskaya²,

Spear³

2009

Physiology & Behavior

177

150

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Adolescence is associated with potentially stressful challenges, and adolescents may differ from adults in their stress responsivity. To investigate possible age-related differences in stress responsiveness, the consequences of repeated restraint stress (90 min/day for 5 days) on anxiety, as indexed using the elevated plus-maze (EPM) and modified social interaction (SI) tests, were assessed in adolescent and adult Sprague-Dawley male and female rats. Control groups at each age included non-stressed and socially deprived animals, with plasma corticosterone (CORT) levels also measured in another group of rats on days 1 and 5 of stress (sampled 0, 30, 60, 90, and 120 min following restraint onset). While repeatedly restrained animals exhibited similar anxiety levels compared to non-stressed controls in the EPM, restraint stress increased anxiety at both ages in the SI test (as indexed by reduced social investigation and social preference). Daily weight gain measurements, however, revealed more marked stress-related suppression of body weight in adolescents versus adults. Analysis of stress-induced increases in CORT likewise showed that adolescents demonstrated less habituation than adults, embedded within typical sex differences in CORT magnitude (females greater than males) and age differences in CORT recovery (adolescents slower than adults). Despite no observable age-related differences in the behavioral response to restraint, adolescents were more sensitive to the repeated stressor in terms of physiological indices of attenuated weight gain and habituation of stress-induced CORT.

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“…Previous studies provided rather mixed results regarding anxiety, which may be due to factors such as local degree and anatomical extent of lesion: Studies with more severe 5HT lesions (81-99%) led to anxiolytic effects (Briley et al, 1990;Olausson et al, 2001), rather moderate lesions (20-48%; Harro et al, 2001;Gurtman et al, 2002) showed anxiogenic effects, and intermediate lesions showed no effects (54-81%; Andrade and Graeff, 2001;Sommer et al, 2001;Netto et al, 2002;Rex et al, 2003). Interestingly, effects on anxiety-related behavior became also visible there, when rats were challenged with additional stressors (Andrade and Graeff, 2001;Netto et al, 2002). In these studies, lesion techniques that lead to global losses of central 5HT were used.…”

Section: Discussionmentioning

confidence: 99%

Neurochemical and behavioral consequences of striatal injection of 5,7-dihydroxytryptamine

Ludwig

Schwarting

2007

Journal of Neuroscience Methods

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Anxiogenic effect of median raphe nucleus lesion in stressed rats

Cited by 48 publications

References 32 publications

Severely impaired hippocampal neurogenesis associates with an early serotonergic deficit in a BAC α-synuclein transgenic rat model of Parkinson's disease

Severely impaired hippocampal neurogenesis associates with an early serotonergic deficit in a BAC α-synuclein transgenic rat model of Parkinson's disease

Social and non-social anxiety in adolescent and adult rats after repeated restraint

Neurochemical and behavioral consequences of striatal injection of 5,7-dihydroxytryptamine

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