Blockade of adenosine A2A receptors inhibits Tremulous Jaw Movements as well as expression of zif-268 and GAD65 mRNAs in brain motor structures

Kosmowska, Barbara; Ossowska, Krystyna; Wardas, Jadwiga

doi:10.1016/j.bbr.2021.113585

Cited by 3 publications

(3 citation statements)

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“…TJMs are triggered by similar conditions that lead to parkinsonism in humans e.g., by striatal DA depletion (for example by tetrabenazine and reserpine) and acute or subchronic administration of typical antipsychotics (haloperidol and pimozide) [27,39], and are suppressed by known antiparkinsonian drugs, including L-DOPA and DA agonists, as well as by DBS of the STN [39][40][41][42][43]. Multiple studies have demonstrated that TJMs depend on the ventrolateral striatum, but the involvement of both "indirect" striatopallidal and "direct" striatonigral GABAergic downstream pathways has also been suggested [35,39,[44][45][46][47].…”

Section: Pd Tremormentioning

confidence: 99%

“…Tetrabenazine (TBZ), a reversible type 2 vesicular monoamine transporter (VMAT) inhibitor, was dissolved in 20% DMSO in 0.9% NaCl (1N HCl was added to get the drug completely into solution, according to [61,62]; final pH = 3.5) and given acutely at a dose of 2 mg/kg. This treatment procedure was based on previous experiments that employed the pimozideinduced TJMs model [47,63], see also Supplementary Data Figures S1-S3. Zolpidem hemitartare (synthesized and provided by Dr. M. Marcinkowska, Jagiellonian University, Medical College, Kraków, Poland), according to the previously reported procedure [64], a positive allosteric modulator of GABA-A receptors containing α1 subunit was dissolved in sterile redistilled water and administered acutely at doses of 0.34, 0.67, 1.01 mg/kg.…”

Section: Compoundsmentioning

confidence: 99%

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GABA-A Alpha 2/3 but Not Alpha 1 Receptor Subunit Ligand Inhibits Harmaline and Pimozide-Induced Tremor in Rats

et al. 2023

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Treatment of tremors, such as in essential tremor (ET) and Parkinson’s disease (PD) is mostly ineffective. Exact tremor pathomechanisms are unknown and relevant animal models are missing. GABA-A receptor is a target for tremorolytic medications, but current non-selective drugs produce side effects and have safety liabilities. The aim of this study was a search for GABA-A subunit-specific tremorolytics using different tremor-generating mechanisms. Two selective positive allosteric modulators (PAMs) were tested. Zolpidem, targeting GABA-A α1, was not effective in models of harmaline-induced ET, pimozide- or tetrabenazine-induced tremulous jaw movements (TJMs), while the novel GABA-A α2/3 selective MP-III-024 significantly reduced both the harmaline-induced ET tremor and pimozide-induced TJMs. While zolpidem decreased the locomotor activity of the rats, MP-III-024 produced small increases. These results provide important new clues into tremor suppression mechanisms initiated by the enhancement of GABA-driven inhibition in pathways controlled by α2/3 but not α1 containing GABA-A receptors. Tremor suppression by MP-III-024 provides a compelling reason to consider selective PAMs targeting α2/3-containing GABA-A receptors as novel therapeutic drug targets for ET and PD-associated tremor. The possibility of the improved tolerability and safety of this mechanism over non-selective GABA potentiation provides an additional rationale to further pursue the selective α2/3 hypothesis.

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Section: Pd Tremormentioning

confidence: 99%

Section: Compoundsmentioning

confidence: 99%

GABA-A Alpha 2/3 but Not Alpha 1 Receptor Subunit Ligand Inhibits Harmaline and Pimozide-Induced Tremor in Rats

et al. 2023

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“…Indeed, alterations in the BG may result in Parkinsonism, which is a characteristic syndrome of PD observed as tremors at rest, joint stiffness, bradykinesia-hypokinesia and postural alteration [ 3 , 12 ]. For instance, a type of Parkinsonism (i.e., tremulous jaw movements, TJMs) may be caused by subchronic systemic treatment with the dopamine antagonist haloperidol.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological Characterization of Cerebellar Responses during Exploration and Grooming Behaviors in a Rat Model of Parkinsonism

et al. 2023

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Parkinson’s disease is currently a global public health challenge due to the rapid growth of aging populations. To understand its pathophysiology is necessary to study the functional correlation between the basal ganglia (BG) and the cerebellum, which are involved in motor control. Herein, we explored multiunit electrical activity (MUA) in the cerebellum of rats with induced Parkinsonism as a result of lesions following bilateral placement of electrodes and passing of current in the ventrolateral striatum (VLS). In one control group, the electrodes descended without electrical current, and another group was left intact in VLS. MUA was recorded in Sim B and Crus II lobes, and in the dentate nucleus (DN) during the execution of exploration behaviors (horizontal and vertical) and grooming. The lesioned and sham groups showed a decrease in MUA amplitude in the Crus II lobe compared to the intact group in all recorded behaviors. However, Sim B and DN did not express differences. Both electrical and physical insults to the VLS induced Parkinsonism, which results in less MUA in Crus II during the execution of motor behaviors. Thus, this type of Parkinsonism is associated with a decrease in the amplitude of Crus II.

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Adenosinergic Pathway in Parkinson’s Disease: Recent Advances and Therapeutic Perspective

2023

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Blockade of adenosine A2A receptors inhibits Tremulous Jaw Movements as well as expression of zif-268 and GAD65 mRNAs in brain motor structures

Cited by 3 publications

References 94 publications

GABA-A Alpha 2/3 but Not Alpha 1 Receptor Subunit Ligand Inhibits Harmaline and Pimozide-Induced Tremor in Rats

GABA-A Alpha 2/3 but Not Alpha 1 Receptor Subunit Ligand Inhibits Harmaline and Pimozide-Induced Tremor in Rats

Electrophysiological Characterization of Cerebellar Responses during Exploration and Grooming Behaviors in a Rat Model of Parkinsonism

Adenosinergic Pathway in Parkinson’s Disease: Recent Advances and Therapeutic Perspective

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