An alpha 5-GABAA receptor positive allosteric modulator attenuates social and cognitive deficits without changing dopamine system hyperactivity in rats exposed to valproic acid in utero.
Adriana Jesus Souza, Ícaro Silva Freitas, Dishary Sharmin and 3 others
PMID 39169698WHAT IT FOUND
A drug acting on a specific GABA receptor improved social behaviour in male rats exposed to valproic acid before birth, but not in females, and did not reduce dopamine overactivity.
It is not human autism evidence.
Key findings
01The tested GABA receptor modulator reduced social interaction deficits in male rats exposed to valproic acid before birth, but not in female rats.
02In male rats, the tested GABA receptor modulator showed only a trend toward reversing object recognition deficits (p=0.059), and female rats did not show deficits in this task.
03The tested GABA receptor modulator did not reduce the increased number of spontaneously active dopamine neurons in the ventral tegmental area seen after prenatal valproic acid exposure.
STILL TO COME
How it was doneWhat they found
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What it does not show
The study was done in rats, not people, and the tested compound was not delivered by physical, occupational, or speech therapists. It used a prenatal valproic acid exposure model, so the measured behaviours may not match autistic people's social or communication difficulties. The exact number of rats analysed is not stated, although pups from 10 dams were used. Benefits were mainly seen in male rats; female rats did not show the same social benefit, so sex differences limit generalisation. The object recognition benefit in males was a trend (p=0.059), not a significant result. The dopamine measure did not change, so the behavioural findings do not show a mechanism through dopamine.
Declared interests
The supplied text states one author is a co-inventor or listed on patent applications covering GABAergic ligands and their use in brain disorders. No funding source is stated.
The easy way to misread this
Do not read this as evidence that a GABA receptor drug treats autism in people. The work was done in rats, the social benefit was mainly in males, and the dopamine activity finding was null.