[slaucon]

In a similar vein, I always found it interesting (although frightening) that rabies cause hydrophobia. The theory is that drinking water can wash away the virus from your saliva, inhibiting its ability to spread through bites.

It makes sense that a virus passed through saliva would evolve like this, but I just find it particularly unsettling when a pathogen can effect higher-level behaviors like drinking water (or jumping into water for mantises).

[brookst]

The frightening part is that it’s a cognitive effect. That’s crazy. And it opens the whole “how much of our personality is real versus controlled by microbes” question.

[wizardforhire]

Ship of Theseus now with your own mind.

[gosub100]

Imagine there was a virus or parasite that just made you feel pleasure, all the time, with no tolerance effects?

I wonder what progress has been made in addiction medicine for meds that simply prevent the development of tolerance? If possible, it would fall under the category of harm reduction. Failing the patient to get sober, they could at least continue getting high on the same amount which might prevent their failure to function.

[username135]

Youd have to figure out how to continuously produce dopamine and serotonin, or replicate their effects from the perspective of pleasure. Pretty tall order since they have multiple purposes inside you. Trillion dollar idea though.

[gosub100]

I was more suggesting that if the receptors could be targeted (I have no idea how, just spit-balling) by another agent, then tolerance would perhaps not occur. The addict/user would still need the original drug.

[SturgeonsLaw]

Receptor downregulation plays a key role in maintaining homeostasis within normal brain function, so attempting to intefere with that process is playing a dangerous game, however it is in theory possible, since the effects of receptor activation are separate from the downregulation process, though they are linked.

When a neuron's receptors get strongly activated, that neuron can withdraw receptors from its surface into the interior of the cell (a process call internalisation), and from there either digest the receptors (downregulation) or move the receptors back to the surface of the cell where they resume their typical function (resensitisation). Those processes are potential targets for a tolerance-mitigating drug.

The tricky part is that they are very fundamental processes across all neurons and it would be very hard to target, say, dopaminergic receptors in the nucleus accumbens to ventral tegmental area (the "reward circuit") without also affecting neurons across the entire brain.

The best cure for tolerance is taking a break :) easier said than done, I know.

[emptiestplace]

I appreciate harm reduction but I think any such 'perfect' drug would lead to dehydration / starvation deaths, or at least a lot more people living on the streets.

[brookst]

See also: Infinite Jest

[thaumasiotes]

> I always found it interesting (although frightening) that rabies cause hydrophobia.

Well, there are two potential senses of "hydrophobia".

In its primary use, it means "rabies", and it's not really interesting that rabies would cause that.

In rare cases, it could mean "fear of water", which rabies doesn't cause. Rabies causes pain when swallowing. The pain causes fear through conventional mechanisms.

[sebtron]

I have not checked the sources, but according to Wikipedia [1]:

Rabies has also occasionally been referred to as hydrophobia ("fear of water") throughout its history. It refers to a set of symptoms in the later stages of an infection in which the person has difficulty swallowing, shows panic when presented with liquids to drink, and cannot quench their thirst. Saliva production is greatly increased, and attempts to drink, or even the intention or suggestion of drinking, may cause excruciatingly painful spasms of the muscles in the throat and larynx. Since the infected individual cannot swallow saliva and water, the virus has a much higher chance of being transmitted, because it multiplies and accumulates in the salivary glands and is transmitted through biting.

It seems more than just "pain when swallowing".

[1] https://en.wikipedia.org/wiki/Rabies

[dotancohen]

It does seem like your comment for the most part supports the GP comment, other than the disagreement about the definition of pain.

For what it's worth, I see the word pain as he used it to be a better fit than the word fear, as in phobia.

[wongarsu]

I feel like calling "shows panic when presented with liquids to drink" a fear of water is a perfectly fine shorthand. Even if it might not be a literal fear of all forms of water, only water you are supposed to drink

[withinboredom]

Pain doesn’t cause panic.

[kruffalon]

Sure, I don't know how it works physiologically...

But anecdata at least suggests that being in enough pain can cause panic, but it might do so indirectly so that the fear is created around the inability to think the pain will ever end or at least lessen at least a bit.

[withinboredom]

My leg has been fucked for 15 years. Sometimes it hurts so bad, I’d need narcotics to make it go away. I don’t panic when walking, I just deal with it because I need to get to my destination. If you are thirsty, you will drink through the pain. Panic is something else.

[pockmarked19]

It does.

If I come into the room and stab you with a steak knife every time you drink, and sometimes even if you only think about drinking, you will definitely panic when drinking is brought up in the future, after some time.

Not sure what's wrong with you that you cannot empathize.

[withinboredom]

As someone who has most definitely been in more shit than most humans on this planet, I can empathize just fine.

As I mentioned in a sibling comment, I think you've confused fear with panic. Fear can be conditioned, panic cannot. You can panic from fear, but it is not a guaranteed thing, and often, that panic is long after the fear is gone (aka PTSD).

Panic is an autonomic response to saving yourself at all costs. It is not something you "learn" or have "conditioned" into you, and if so, definitely not over the course of a few weeks that you have a virus; otherwise we'd all be dead from Covid and go into a panic every time we cough.

Panic is what causes you to drown a person saving you, so that you can breathe. Panic is what causes you to over-correct and steer into a tree. Panic is what causes you to run out of your house, in the middle of winter in pajamas, because there was a spider. Panic has a cause, but it is mindless with the only goal of saving oneself. The action itself is often quite stupid-looking, in hindsight and lack of context.

Most people have never seen a person panic, first-hand. Most people have never panicked. Today's world is largely safe, so it is easy to confuse fear with panic.

[ImPostingOnHN]

Not sure that's comparable to a situation where a virus like Rabies causes someone to inherently fear water, regardless of pain.

[gosub100]

Deep water doesn't cause pain, yet a significant portion of people would panic upon being dropped into it.

[GuB-42]

It is probably a bit of both.

From the same Wikipedia article

> symptoms can include slight or partial paralysis, anxiety, insomnia, confusion, agitation, abnormal behavior, paranoia, terror, and hallucinations

There is more than just pain here. The virus changes the host behavior, making it more aggressive, so it is very possible that it also promotes a panic reaction to pain.

[amelius]

On the other hand, without saliva the virus cannot spread, and you need water to have saliva.

[llamaimperative]

Evolution has already done the math on this

(Or more precisely, it’s already doing the math, and the current answer is that hydrophobia is the better solution [for rabies’ purposes])

[amelius]

The particular math used might get stuck in a local optimum ...

[llamaimperative]

Possible but unlikely in this case

[serf]

without a big genetic assay isn't it virtually impossible to know whether or not the trait (hydrophobia) persisted due to the symptom itself rather than just a correlated advantageous mutation that brought along hydrophobia as a happy coincidence?

if we need to continue the flawed math analogy; evolution has always done pretty imprecise cocktail-napkin math, even if it has been wildly successful at it.

[DontchaKnowit]

Really that is not how evolution works

[DontchaKnowit]

That is extremely far fetched