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Review Dopamine/adenosine interactions related to locomotion and tremor in animal models: possible relevance to parkinsonism. 2008
Salamone JD, Ishiwari K, Betz AJ, Farrar AM, Mingote SM, Font L, Hockemeyer J, Müller CE, Correa M. · Behavioral Neuroscience Division, Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. · Parkinsonism Relat Disord. · Pubmed #18585081 No free full text.
Abstract: Adenosine A(2A) antagonists can exert antiparkinsonian effects in animal models. Recent experiments studied the ability of MSX-3 (an adenosine A(2A) antagonist) to reverse the locomotor suppression and tremor produced by dopamine antagonists in rats. MSX-3 reversed haloperidol-induced suppression of locomotion, and reduced the tremulous jaw movements induced by haloperidol, pimozide, and reserpine. Infusions of MSX-3 into the nucleus accumbens core increased locomotion in haloperidol-treated rats, but there were no effects of infusions into the accumbens shell or ventrolateral neostriatum. In contrast, MSX-3 injected into the ventrolateral neostriatum reduced pimozide-induced tremulous jaw movements. Dopamine/adenosine interactions in different striatal subregions are involved in distinct aspects of motor function.
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Article The GABA uptake inhibitor beta-alanine reduces pilocarpine-induced tremor and increases extracellular GABA in substantia nigra pars reticulata as measured by microdialysis. 2004
Ishiwari K, Mingote S, Correa M, Trevitt JT, Carlson BB, Salamone JD. · Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. · J Neurosci Methods. · Pubmed #15589332 No free full text.
Abstract: Substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia that receives GABAergic projections from neostriatum and globus pallidus. Previous research has shown that local pharmacological manipulations of GABA in SNr can influence tremulous jaw movements in rats. Tremulous jaw movements are defined as rapid vertical deflections of the lower jaw that resemble chewing but are not directed at a particular stimulus, and evidence indicates that these movements share many characteristics with parkinsonian tremor in humans. In order to investigate the role of GABA in motor functions related to tremor, the present study tested the GABA uptake blocker beta-alanine for its ability to reduce pilocarpine-induced tremulous jaw movements. In a parallel experiment, the effect of an active dose of beta-alanine on dialysate levels of GABA in SNr was assessed using microdialysis methods. GABA levels in dialysis samples were measured using high performance liquid chromatography with electrochemical detection. beta-Alanine (250-500 mg/kg) significantly reduced tremulous jaw movements induced by pilocarpine (4.0 mg/kg). Moreover, systemic administration of beta-alanine at a dose that reduced tremulous jaw movements (500 mg/kg) resulted in a substantial increase in extracellular levels of GABA in SNr compared to the pre-injection baseline. Thus, the present results are consistent with the hypothesis that GABAergic tone in SNr plays a role in the regulation of tremulous jaw movements. This research may lead to a better understanding of how parkinsonian symptoms are modulated by SNr GABA mechanisms.
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