0.5 mg/kg seems like a big dose of amphetamine! A 150 lb person would receive >30 mg of dexamphetamine, which is a ton for a person who doesn’t take stimulants regularly (hopefully, for experimental control, none of the subjects are stimulant users).

I’ve only read the abstract.

First, this experiment was done in human patients (17 depressed, 20 healthy controls).
They give the amphetamine not to induce “depression” but to simulate dopaminergic stimulation, which activates serotonin-releasing neurons downstream.

They also administer a radioactive ligand for the serotonin 5-HT2a receptor, which is one of the “targets” of released serotonin. By measuring how much radioactivity is displaced after the amphetamine-induced serotonin flood, they can measure approximately how much serotonin must have been released.

I’m not in this field, but some questions this study raises for me include:

• does depression alter the activity of amphetamine.
• are 5HT2a receptors and Dopamine Transporters (amphetamine target) differently expressed in depression.
• are the inhibitory autoreceptors for serotonin (eg 5HT1 a/b/d) expressed in different proportion to 5HT2a receptors in depression?

Though the sigma receptors are unusually promiscuous, binding to a wide variety of chemical classes. So sigma receptor activity may just be a shared off-target.