Neuropsychopharmacology really isn't a well-defined and regimented method or direction of scientific study: anybody who does research in neuropsychopharmacology would probably identify themselves primarily as a neuroscientist
or perhaps a psychiatry
researcher. Furthermore, it is not simply the study of psychoactive drugs per se
, thought that aspect is a major focus; rather, the ultimate goal in studying neuropsychopharmacology is to understand the workings of the mind
in terms of the chemo-anatomy
of the brain.
This may sound like a trivial and obligatory thing to study (wouldn't you hope that your doctor to knows exactly what your Prozac is doing to your brain?*), but it is technically and conceptually an extraordinary undertaking.
It requires that the sub-cellular-level actions of a psychoactive drug (such as Prozac) or naturally occurring neurochemical substance (such as glutamate or dopamine) be reconciled to the systems-level actions it has on a neural circuit which could span dozens of distinct brain areas -- all in the context of the mental functions that the circuit subserves. In other words, it requires knowing about the actions of neurochemicals from the most minute, biochemical level of detail the most global, psychological level. This is hardly a trivial task; trying to figure out the workings of a psychoactive substance at any one level alone is a tour de force, usually requiring years of experimentation and scientific debate.
There are a few drugs that are relatively well understood in terms of their actions on neural circuits and the change in behavior that results. I'll illustrate one below -- however, I must apologize for the scads of neuroanatomy and other jargon. It's really the only way for me to be even remotely accurate, especially considering that the story I tell below is rather condensed and summarized, and skips over some sticky details that have yet to be fully worked out.**
So . . .
Parkinson's Disease is characterized in general by a dysfunction in movement or motor functioning; its symptoms can include the overabundance of motor activity, such as rigidity, tremors or spasmodic movements, or as a paucity of motor activity, such as the inability to initiate movements, shuffling gait or slowness in movements. One well documented cause of Parkinson's involves the interactions between the basal ganglia and the dopamine-containing cells of a brainstem region called the substantia-nigra.
Specifically, (here comes the jargon) these dopaminergic cells of the substantia nigra send dopamine input to the caudate nucleus and the putamen -- the "input" part of the basal ganglia which receives massive projections from the cerebral cortex. This dopaminergic input is excitatory, thus, when cells of the substantia nigra die, the caudate and putamen are less active overall. This caudate and putamen provide direct inhibitory input to another part of the basal ganglia, the internal portion of the globus pallidus (GPi). The GPi, in turn, provides direct output -- also inhibitory -- to the ventrolateral thalamus, a thalamic nucleus which (along with certain parts of the cerebral cortex) is heavily involved in the control of movement.
Thus, loss of excitation in the caudate in putamen leads to disinhibition of the GPi, leading to increased inhibition of the ventrolateral thalamus, leading to a paucity of movement which is typically seen in Parkinson's patients.
Treatment with a chemical called L-dopa can temporarily alleviate these specific symptoms. L-dopa is a precursor to dopamine, and, when taken orally, it can enter the blood and be taken into neurons, where it is converted into dopamine***. Thus administration of L-dopa causes an increased production of dopamine, leading to an increased amount of dopamine released into the caudate and putamen, leading (eventually) to increased activity in the ventrolateral thalamus and a restoration of normal motor activity.
As I said, this is the Reader's Digest version of the story, but it is for the most part correct. The most interesting part of this (I find) is that L-dopa therapy for Parkinson's did not evolve based on knowledge of the disease. Only after scientists and doctors realized that L-dopa alleviated the symptoms of Parkinson's did they begin to understand the brain mechanisms behind the disease -- and behind movement in general. The fact that the drug worked is what motivated the study of dopamine in these forebrain circuits and eventually led to the understanding of the motor circuits described above.
Oh, and that thing I said about Prozac -- yeah, down there in the first footnote* -- it's true to some degree. Without going into the gory details, it turns out that while Prozac’s main pharmacological action begins only hours after the drug is consumed, it can take weeks of taking the drug before a patient feels better. Why is this? What is the drug doing two weeks later that it isn't doing before that? This really isn't known -- though it is being studied like hell in the hope that it will, first of all, uncover the true actions of the drug but, more importantly, will also tell neuroscientists something about mood, depression and how they are mediated in the brain.
*Oh, by the way: he doesn't. Read below for the full skinny.
**Also: some of this is covered roughly in other nodes, though AFAIK there isn't any real neuroanatomy in any of them. If someone finds that there's already a node about this, then I'll be glad to remove this portion of the WU.
***Why, you may ask, do you give them a precursor of dopamine instead of just pure dopamine? Briefly explained: the brain contains an enormous volume of supporting cell types, and these cells are very, very picky about what substances they allow into the neurons. This system of filtration by supporting cells is often referred to as the blood brain barrier. As it turns out, the blood brain barrier does not allow dopamine to cross from the blood into neurons, but it will allow L-dopa. Go figure.