Home
Resources
Publications
Molecular Mechanisms of the Antispasticity Effects of Baclofen on Spinal Ventral Horn Neurons

Molecular Mechanisms of the Antispasticity Effects of Baclofen on Spinal Ventral Horn Neurons

Tadakazu Abe, Wataru Taniguchi, Naoko Nishio, Terumasa Nakatsuka, Munehito Yoshida, Hiroshi Yamada

Neuroreport. 2019 Jan 2;30(1):19-25.

PMID: 30371538

Abstract:

Background:
Baclofen is a lipophilic γ-aminobutyric acid (GABA) derivative that exhibits strong intrinsic activity and a high affinity for GABAB receptors. Intrathecal baclofen therapy has been used as an antispasticity and muscle relaxant drug in the clinical treatment of patients with severe spasticity. However, the cellular mechanisms of the antispasticity effects of baclofen on the ventral horn neurons of the spinal cord are unknown.
Objective:
We examined the action of baclofen on excitatory synaptic transmission in ventral horn neurons in the rat spinal cord by whole-cell patch-clamp recordings.
Results:
Baclofen significantly reduced the frequency and amplitude of miniature excitatory postsynaptic currents. The reduction in miniature excitatory postsynaptic current frequency was particularly strong, indicating presynaptic inhibition by baclofen. Moreover, baclofen-induced outward currents in all neurons tested. The baclofen-induced outward currents persisted in the presence of tetrodotoxin and glutamate receptor antagonists and were diminished in the presence of the postsynaptic intracellular K channel blocker cesium sulfate and the G-protein inhibitor guanosine 5'-(β-thio)diphosphate trilithium salt. These results indicate direct postsynaptic depression mediated by G-protein-activated K channels by GABAB receptors on ventral horn neurons. The baclofen-induced outward currents and the inhibitory effects on spontaneous excitatory postsynaptic currents were blocked by the selective GABAB receptor antagonist CGP35348.
Conclusion:
Baclofen may have both presynaptic and postsynaptic capacity to inhibit synaptic transmission in ventral horn neurons by GABAB receptors. These cellular mechanisms may induce the antispasticity effects of intrathecal baclofen therapy in the spinal cord.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP10294549	Cesium sulfate		10294-54-9	Price
AP97952368	Guanosine 5′-[β-thio]diphosphate trilithium salt		97952-36-8	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: