Discover how amphetamine’s grip on the brain’s reward system differs between males and females, potentially reshaping addiction treatments.
– by Marv
Note that Marv is a sarcastic GPT-based bot and can make mistakes. Consider checking important information (e.g. using the DOI) before completely relying on it.
Amphetamine induces sex-dependent loss of the striatal dopamine transporter in sensitized mice.
Bagalkot et al., eNeuro 2023
DOI: 10.1523/ENEURO.0491-23.2023
Oh, What a Surprise: Drugs Do Things to Your Brain!
Brace yourselves, folks, for the shocking revelation that the dopamine transporter (DAT), the brain’s diligent dopamine recycler, gets a bit wonky when you repeatedly party with amphetamine (Amph). Who would’ve thought that abusing a psychostimulant could lead to something more than just a good time, right?
Our intrepid scientists, armed with their HA-epitope tagged DAT mice (because why use regular mice when you can have designer ones?), embarked on a wild 14-day Amph-sensitization bender. The result? On day 14, these mice were zooming around their cages like furry little race cars, especially the males, who just couldn’t seem to sit still for a whole hour.
But wait, there’s more! It turns out that the male mice, in their stimulant-fueled fervor, managed to misplace about 30-60% of their DAT proteins in the striatum. The females, on the other hand, kept their DATs mostly intact. Who knew that male mice were so careless?
And because we love details, the researchers also noted that Amph didn’t just make the DAT proteins play hide and seek; it also messed with the speed of dopamine transport in the boys’ brains. But fear not, the affinity of DAT for dopamine (Km) remained as steadfast as ever.
Now, for the pièce de résistance: the male mice’s DATs were caught red-handed hanging out with the endosomal protein VPS35 after an Amph challenge. It’s like they were planning a secret escape from the cell surface all along! And guess what blocked this grand escape? A cocktail of inhibitors that would make any biochemist swoon.
But here’s the kicker: the DATs didn’t just vanish into thin air; they were actually being degraded in the nucleus accumbens, a brain region that’s like Grand Central Station for reward and addiction. Apparently, the dorsal striatum didn’t get the memo, because it was business as usual over there.
Significant Statement: In a groundbreaking display of the obvious, we’ve discovered that Amph, a well-known party drug, actually has long-term effects on the brain’s dopamine system. Specifically, it sends the DAT proteins in male mice on a one-way trip to the cellular underworld, a phenomenon that’s as gender-specific as it is region-specific. And all this in a mouse model that’s just a whisker away from mimicking human addiction. Science, ladies and gentlemen!