Credit score: Science Advances (2025). DOI: 10.1126/sciadv.ads4441
Cocaine, a drug of abuse, prompts only a portion—10% to twenty%—of the neurons within the mind’s nucleus accumbens, a vital area linked to motivation and dependancy. Although small in numbers, this activated neuronal inhabitants strongly controls drug-related conduct via downstream modifications in gene expression, nerve synapses, neural circuitry and neural perform that result in behavioral change, together with dependancy.
In a examine revealed in Science Advances, College of Alabama at Birmingham researchers led by Kasey Brida and Jeremy Day, Ph.D., report that the secreted glycoprotein reelin is a marker for these nucleus accumbens neurons which have been activated by cocaine.
With a purpose to determine whether or not reelin contributes to drug-related mobile and behavioral modifications, the staff developed a CRISPR interference technique to focus on and cut back the expression of the reelin gene in nucleus accumbens neurons.
Knockdown of reelin in rats decreased gene expression related to activation by cocaine, altered expression of ion channels associated to neuronal excitability and impaired excitability of nucleus accumbens neurons. The knockdown additionally abolished cocaine-induced behavioral modifications in motion and place desire, and it dampened cocaine self-administration by the rats.
“Together, these results identify reelin as a stable marker of cocaine-sensitive neurons and reveal a key role for reelin in the transcriptional, electrophysiological and behavioral properties of cocaine-induced striatal plasticity,” mentioned Brida, a graduate scholar in Day’s UAB Division of Neurobiology lab.
“These findings highlight an opportunity for high-precision manipulation of reward circuitry using reelin-based tools, reveal the necessity of reelin in the cellular response to cocaine and implicate the reelin signaling pathway as a potential therapeutic target for cocaine use disorder.”
Prior research have demonstrated that cocaine’s results on the nucleus accumbens happen in medium spiny neurons, that are the principal neuronal sort on this mind area and specific receptors for the neurotransmitter dopamine. The researchers recognized reelin as a marker of cocaine-activated medium spiny neurons by leveraging unbiased single-nucleus RNA sequencing datasets beforehand collected after cocaine publicity.
Greater than 80% of activated medium spiny neurons within the nucleus accumbens expressed reelin mRNA, with common expression about 10 instances better in comparison with neurons that weren’t activated by cocaine. In addition they confirmed that reelin is enriched in a subpopulation of medium spiny neurons in each the rat and human mind.
Researchers then used the CRISPR interference knockdown of reelin expression to determine its influences on medium spiny neuron physiology and drug-related behaviors. The CRISPR interference system was carried by lentiviruses injected immediately into the nucleus accumbens within the rat mind. The knockdown experiments collectively urged that reelin expression permits neurons to be excitable and provoke sign transduction cascades that cocaine makes use of to form neuronal perform over longer timescales, Brida says.
Reelin has lengthy been identified to be essential for the event of mammalian brains throughout embryogenesis, and it’s also identified to play a task in synaptic plasticity and performance within the grownup mind. Reelin additionally has hyperlinks to various neuropsychiatric problems. Nonetheless, the discovering that mRNA for the protein reelin was enriched in medium spiny neurons that have been activated by cocaine was surprising, Brida and Day say.
Extra info:
Kasey L. Brida et al, Reelin marks cocaine-activated striatal neurons, promotes neuronal excitability, and regulates cocaine reward, Science Advances (2025). DOI: 10.1126/sciadv.ads4441
Supplied by
College of Alabama at Birmingham
Quotation:
A glycoprotein marks cocaine-activated mind neurons and regulates cocaine reward (2025, June 9)
retrieved 9 June 2025
from https://medicalxpress.com/information/2025-06-glycoprotein-cocaine-brain-neurons-reward.html
This doc is topic to copyright. Other than any honest dealing for the aim of personal examine or analysis, no
half could also be reproduced with out the written permission. The content material is supplied for info functions solely.
