Bimodal effect of amphetamine on motor behaviors in C57BL/6 mice

Yates, Jonathan W.; Meij, Johanna T. A.; Sullivan, Juliana; Richtand, Neil M.; Yu, Lei

doi:10.1016/j.neulet.2007.09.011

Cited by 56 publications

(47 citation statements)

References 23 publications

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“…injection of amphetamine did not elicit any response in wild-type mice, we increased the dose of amphetamine to 3 mg/kg in Rhes −/− mice, which produced greater locomotor activity and stereotypy response relative to wild-type controls, which showed a slight but significant increase in locomotion and a slight decrease in stereotypic behaviors ( Fig. 2, E-H, n = 8/group, mixed sex ratio), consistent with a previous report (44). The basal (spontaneous) locomotor activity before amphetamine administration appeared similar in both wild-type and Rhes −/− mice ( Fig.…”

Section: Resultssupporting

confidence: 91%

RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network (“Rhesactome”) in the striatum

et al. 2016

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The striatum of the brain coordinates motor function. Dopamine-related drugs may be therapeutic to patients with striatal neurodegeneration, such as Huntington's disease (HD) and Parkinson's disease (PD), but these drugs have unwanted side effects. In addition to stimulating the release of norepinephrine, amphetamines, which are used for narcolepsy and hyperactivity disorder (ADHD), trigger dopamine release in the striatum. The GTPase Ras homolog-enriched in the striatum (Rhes) inhibits dopaminergic signaling in the striatum, is implicated in HD, and has a role in striatal motor control. We found that the guanine nucleotide exchange factor (GEF) RasGRP1 inhibited Rhes-mediated control of striatal motor activity in mice. RasGRP1 stabilized Rhes, increasing its synaptic accumulation in cultured striatal neurons.. Whereas partially Rhes-deficient (Rhes +/− ) mice had an enhanced locomotor response to amphetamine, this phenotype was attenuated by coincident depletion of RasGRP1. By proteomic analysis of striatal lysates from Rhes-heterozygous mice with wild-type or partial or complete knockout of Rasgrp1, we identified a diverse set of Rhes-interacting proteins, the "Rhesactome," and determined that RasGRP1 ** This manuscript has been accepted for publication in Science Signaling. This version has not undergone final editing. Please refer to the complete version of record at http://www.sciencesignaling.org/. The manuscript may not be reproduced or used in any manner that does not fall within the fair use provisions of the Copyright Act without the prior, written permission of AAAS.

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Section: Resultssupporting

confidence: 91%

RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network (“Rhesactome”) in the striatum

et al. 2016

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“…We therefore asked whether amphetamine treatment could also recover mood disturbance in EAE mice, but we could not assess behavior in the treated mice. Indeed, in our experimental condition, about 70 % of the mice showed hypo-locomotion (number of the line crossing between the LD compartments: EAE amphetamine: 1.58 ± 0.47, n = 17; EAE vehicle: 3.78 ± 0.42, n = 14; unpaired T test ** p = 0.0021, data not shown), in accordance with the literature reporting that amphetamine affects locomotion in a dose- and time-dependent manner [64, 65]. …”

Section: Discussionsupporting

confidence: 90%

Interaction between interleukin-1β and type-1 cannabinoid receptor is involved in anxiety-like behavior in experimental autoimmune encephalomyelitis

Gentile

Fresegna

Musella

et al. 2016

J Neuroinflammation

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BackgroundMood disorders, including anxiety and depression, are frequently diagnosed in multiple sclerosis (MS) patients, even independently of the disabling symptoms associated with the disease. Anatomical, biochemical, and pharmacological evidence indicates that type-1 cannabinoid receptor (CB1R) is implicated in the control of emotional behavior and is modulated during inflammatory neurodegenerative diseases such as MS and experimental autoimmune encephalomyelitis (EAE).MethodsWe investigated whether CB1R could exert a role in anxiety-like behavior in mice with EAE. We performed behavioral, pharmacological, and electrophysiological experiments to explore the link between central inflammation, mood, and CB1R function in EAE.ResultsWe observed that EAE-induced anxiety was associated with the downregulation of CB1R-mediated control of striatal GABA synaptic transmission and was exacerbated in mice lacking CB1R (CB1R-KO mice). Central blockade of interleukin-1β (IL-1β) reversed the anxiety-like phenotype of EAE mice, an effect associated with the concomitant rescue of dopamine (DA)-regulated spontaneous behavior, and DA-CB1R neurotransmission, leading to the rescue of striatal CB1R sensitivity.ConclusionsOverall, results of the present investigation indicate that synaptic dysfunction linked to CB1R is involved in EAE-related anxiety and motivation-based behavior and contribute to clarify the complex neurobiological mechanisms underlying mood disorders associated to MS.

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“…In humans, the greatest amphetamine-induced ligand displacement is seen in the vStr and also in the sensorimotor Str (putamen) (120, 121). Consistent with the greater DA release in vStr in rodents, amphetamine and cocaine at lower doses appear to act preferentially in the vStr to drive hyperlocomotion, while at higher doses they act in the dStr to drive stereotypy (122–124). …”

Section: Regional Differences In Psychotropic Drug Action At Striatalmentioning

confidence: 62%

Heterogeneity in Dopamine Neuron Synaptic Actions Across the Striatum and Its Relevance for Schizophrenia

Chuhma

Mingote

Kalmbach

et al. 2017

Biological Psychiatry

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Brain imaging has revealed alterations in dopamine uptake, release and receptor levels in patients with schizophrenia that have been resolved at the scale of striatal subregions. However, the underlying synaptic mechanisms are at a finer scale. Dopamine neuron synaptic actions vary across the striatum, involving not only variations in dopamine release, but also in dopamine neuron connectivity, cotransmission, modulation and activity. Optogenetic studies have revealed that dopamine neurons release dopamine in a synaptic signal mode, and that the neurons also release glutamate and GABA as cotransmitters, with striking regional variation. Fast glutamate and GABA cotransmission convey discrete patterns of dopamine neuron activity to striatal neurons. Glutamate may function not only in a signaling role at a subset of dopamine neuron synapses, but also in mediating vesicular synergy, contributing to regional differences in loading of dopamine into synaptic vesicles. Regional differences in dopamine neuron signaling are likely to be differentially involved in the schizophrenia disease process, and likely determine the subregional specificity of the action of psychostimulants that exacerbate the disorder, and antipsychotics that ameliorate the disorder. Elucidating dopamine neuron synaptic signaling offers the potential for achieving greater pharmacological specificity through intersectional pharmacological actions targeting subsets of dopamine neuron synapses.

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Bimodal effect of amphetamine on motor behaviors in C57BL/6 mice

Cited by 56 publications

References 23 publications

RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network (“Rhesactome”) in the striatum

RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network (“Rhesactome”) in the striatum

Interaction between interleukin-1β and type-1 cannabinoid receptor is involved in anxiety-like behavior in experimental autoimmune encephalomyelitis

Heterogeneity in Dopamine Neuron Synaptic Actions Across the Striatum and Its Relevance for Schizophrenia

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