text.skipToContent text.skipToNavigation

{{ addToCartData.mixPtRmWarning }}

Möchten Sie fortfahren?

{{requestQuote.productName}}; {{requestQuote.form.productCode}}

Vielen Dank

Wir werden in Kürze auf Ihre Anfrage antworten.

Something went wrong, please try again later.

Großbestellung
Wenn nicht, klicken Sie auf „Abbrechen“. Sie können diesen Artikel auch für später speichern.
Abbrechen
Wenn nicht, klicken Sie auf „Abbrechen“. Sie können diesen Artikel auch für später speichern.
Abbrechen

Identifying dopamine-regulating ion channels a ‘major step’ towards new mental illness drugs

no image

 

Ion channel research from the University of Washington Medical School has shed new light on the workings behind dopamine release. The findings could lead to better drugs for depression and other conditions - including schizophrenia, addiction, and autism spectrum disorder.

 

Scientists have taken a ‘major step’ towards better developing mental illness treatments by successfully manipulating two ion channels that control dopamine release.

 

The University of Washington Medical School researchers found that switching off the Kv4.3 channel regulating slower – or ‘tonic’ – dopamine release made mice more motivated.

 

Meanwhile, switching off the BKCa1.1 channel responsible for more rapid, ‘phasic’, activity made them quicker to complete experimental tasks.

 

The findings shed new light onto the mechanisms behind dopamine release - and may be a first step towards developing drugs that target ion channels in order to treat conditions like depression, addiction, schizophrenia and autism spectrum disorder.

 

“This is what we've been working toward for some time: to understand how dopamine signals are regulated so that we can come up with better therapeutics,” said study co-author Larry S. Zweifel.

 

“They may not target these specific channels, but now that we're beginning to get a handle on the mechanism, we might be able to find other players in the process that make for better targets.”

 

The Washington team showed that disrupting Kv4.3 and BKCa1.1 through genetically altering laboratory mice changes the way they behave by “differentially affect(ing) action potential firing patterns and neurotransmitter release” in the ventral tegmental area (VTA) of the midbrain.

 

“(Those) two ion channels… regulate the pattern of dopamine neuron firing and dopamine release on different time scales to influence separate phases of reinforced behavior in mice,” they said, adding: “These data demonstrate that disruption of intrinsic regulators of neuronal activity differentially affects dopamine dynamics during reinforcement and extinction learning.”

 

Through experiments where the mice were rewarded with food by pressing a lever correctly, the researchers found that removing the channel that controls tonic activity resulted in the mice entering a hypertonic flow. This, in turn, created an increased motivational state that encouraged the animals to reattempt their tasks.

 

When the researchers removed the ion channel controlling phasic dopamine release, it increased transient high levels of dopamine in response to specific events – causing the mice to learn tasks faster.

 

Given that humans also possess hundreds of ion channels that regulate the chemical and hormonal processes behind behaviour and mood, Zweifel said the results may hold the key to “improving cognitive function, for example, in patients who have learning disabilities”.

 

They could also help with “increasing motivation in individuals who have depression, where you have a reduced motivational state”, and pave the way for numerous new drug candidates to be tested in clinical trials.

 

“We're hoping that's ultimately what we can do," Zweifel said.

 

The findings of the research – involving 17 scientists from Zwiefel’s laboratory supervised by lead author Barbara Juarez – are published in the journal Science Advances.

 

Juarez is now a professor at the University of Maryland School of Medicine in Baltimore. 

 

 

LGC Standards - for all your research chemical and drug discovery needs

 

LGC standards’ TRC brand has more than 40 years’ experience working through some of the most complex synthetic pathways to deliver you high quality research chemicals. We have a large portfolio  of API, bioactive molecules and SILS, as well as synthetic chemistry tools such as building blocks and linkers.

 

Our TRC range includes many unique molecules for research into mental disorders and neurodegenerative diseases, and we provide wide- ranging chemicals for research into depression - including modulators of 5-HT, GABA and dopamine receptors. And, if you can’t find the chemical you need, our skilled team of synthetic chemics would relish the challenge of designing it for you!

 

Email info.trc@lgcgroup.com for more details. 

 

To support neurobiology in general, ATCC offer a large collection of in vitro tools, including NPC derived from normal and Parkinson’s donors, LRRK2 KI lines, Schwann cells, >70 brain lines.

 

Achtung, Zeitlimit!

Ihre Punchout-Sitzung läuft ab in 1 Min. 59 Sek.

Wählen Sie „Sitzung fortführen“, um Ihre Sitzung zu verlängern