Want to be weirded out? Study the central nervous system. I started off my med-chem career in CNS drug discovery, and it's still my standard for impenetrability. There's a new paper in Science, though, that just makes you roll your eyes and look up at the ceiling.
The variety of neurotransmitters is well appreciated - you have all these different and overlapping signaling systems using acetylcholine, dopamine, serotonin, and a host of lesser-known molecules, including such oddities as hydrogen sulfide and even carbon monoxide. And on the receiving end, the various subtypes of receptors are well studied, and those give a tremendous boost to the variety of signaling from a single neurotransmitter type. Any given neuron can have several of these going on at the same time - when you consider how many different axons can be sprawled out from a single cell, there's a lot of room for variety.
That, you might think, is a pretty fair amount of complexity. But note also that the density and population of these receptors can change according to environmental stimuli. That's why you get headaches if you don't have your accustomed coffee in the morning (you've made more adenosine A2 receptors, and you haven't put any fresh caffeine ligand into them). Then there are receptor dimers (homo- and hetero-) that act differently than the single varieties, constituitively active receptors that are always on, until a ligand turns them off (the opposite of the classic signaling mechanism), and so on. Now, surely, we're up to a suitable level of complex function.
Har har, says biology. This latest paper shows, by a series of experiment in rats, that a given population of neurons can completely switch the receptor system it uses in response to environmental cues:
Our results demonstrate transmitter switching between dopamine and somatostatin in neurons in the adult rat brain, induced by exposure to short- and long-day photoperiods that mimic seasonal changes at high latitudes. The shifts in SST/dopamine expression are regulated at the transcriptional level, are matched by parallel changes in postsynaptic D2R/SST2/4R expression, and have pronounced effects on behavior. SST-IR/TH-IR local interneurons synapse on CRF-releasing cells, providing a mechanism by which the brain of nocturnal rats generates a stress response to a long-day photoperiod, contributing to depression and serving as functional integrators at the interface of sensory and neuroendocrine responses.
This remains to be demonstrated in human tissue, but I see absolutely no reason what the same sort of thing shouldn't be happening in our heads as well. There may well be a whole constellation of these neurotransmitter switchovers that can take place in response to various cues, but which neurons can do this, involving which signaling regimes, and in response to what stimuli - those are all open questions. And what the couplings are between the environmental response and all the changes in transcription that need to take place for this to happen, those are going to have to be worked out, too.
There may well be drug targets in there. Actually, there are drug targets everywhere. We just don't know what most of them are yet.