SUMMARY: Using a little bit of drug does not make those feel-good or high-feeling receptors increase in number. Either before or after.
From the paper: (started this analogy yesterday, should maybe have kept it) I think it's more like if you had never had spicy food, and put a little squirt of tobasco on your food, you'd find it enhanced the experience. The next time you put it on your food you drool before you even eat--your behavior shows you're sensitized to the smell. Maybe you stomp your feet in anticipation. But if you were then given half a bottle on your enchilada, you would throw up and cry and the snot would pour.
If instead you gradually increase the tobasco dose, you find you continue to drool when you smell it, but by the time you get to half-bottle territory, you don't vomit or scream.
The sensitization has less to do with regulation of receptors in response to amphetamine, and more about readouts for researchers. The sensitization is in a tiny part of a tiny brain region involved with motion, it's not something that happens for every dopamine process, I don't think.
Using my analogy, the researchers chose foot stomping to readout sensitization. Conveniently, it uses the same transmitter your tongue does for pain. That means if it's too hot on your tongue, it'll blow out those nerves, AND the nerves that move your feet. As long as the feet are moving, they know your tongue is OK. So when they ramp up to high doses, you still stomp your feet, showing you everything is as it should be, and not fried. That's it, see? Why do they need pages of this stuff? I think it matters for researchers who give speed to rats, and that's it. But it's important for us to have, mainly so we can criticize the papers where people gave speed to rats and didn't taper up the massive doses, like this paper told them to.
That's in the paper. For the anecdotes, the paper does not support anything like what was mentioned. They are NOT describing potentiation of later doses by small doses. If anything the paper describes diminished effects by taking smaller doses earlier in time. The sensitization they described is to behavior associated with anticipating the drug (it involves receptors too). Forever on now, I will catch the occasional odor of dollar bill and flashback to cocaine days. That means a tiny tiny physiological change, slight quickening of my heart beat, in response to a drug association I had years ago. I am sensitized to cocaine. But if I got a baggie tonight, it wouldn't make a difference if I did a little bump and saved the rest for Monday on the quality or intensity of the high.
So really this paper doesn't help us end-user druggies any. The feeling we like from our drugs uses receptors, and too much will make the receptors go down in number. Using a little bit of the drug does NOT make those receptors increase in number. The rest of our brain has thoughts about drugs, and those use transmitters and receptors too, but thinking about cocaine won't make all the cocaine-thought receptors go down in number. In fact, using a little bit of cocaine will make the cocaine-thought receptors increase a whole lot. But not the ones that respond to the actual drug. Sadly.
There's a flip-side that might relate to drug breaks. Because you are sensitized to a drug, going to zero might be better than doing a small amount. Getting that whiff of drug cues strong reactions, in anticipation; and if your drug-feeling receptors are where they were, they won't feel the small dose, get angry, and then you relapse. So sensitization is part of why abstinence for a long time is often best.
