In an interesting discussion of the emerging scientific view of dopamine function in the brain, Natalie Angier explains that notions of dopamine as the pleasure-reward transmitter are giving way to an understanding of dopamine involvement in salience-detection and motivation:
If you’ve ever had a problem with rodents and woken up to find that mice had chewed their way through the Cheerios, the Famous Amos, three packages of Ramen noodles, and even that carton of baker’s yeast you had bought in a fit of “Ladies of the Canyon” wistfulness, you will appreciate just how freakish is the strain of laboratory mouse that lacks all motivation to eat.
The mouse is physically capable of eating. It still likes the taste of food. Put a kibble in its mouth, and it will chew and swallow, all the while wriggling its nose in apparent rodent satisfaction.
Yet left on its own, the mouse will not rouse itself for dinner. The mere thought of walking across the cage and lifting food pellets from the bowl fills it with overwhelming apathy. What is the point, really, of all this ingesting and excreting? Why bother? Days pass, the mouse doesn’t eat, it hardly moves, and within a couple of weeks, it has starved itself to death.
This leads me to think about patients for whom the connection between pleasure/pain and motivation is so thoroughly severed that one is tempted to wonder about the possibility of neurological damage. I am by no stretch of the imagination a reductionist, but we do know that CNS injury sometimes results in impaired motivation. The drug addict who has been beating the crap out of the dopamine systems in his brain often ends up with diminished motivation. It doesn't seem unreasonable to think that years of stress and anxiety can also result in the sort of damage that impairs motivation. Even with the most elaborate contingency cocktails, some patients remain passive observers of their own crumbling lives, unable to engage in the obvious simple acts that will reap rewards or avert suffering.
I'm not suggesting that lack of motivation is always or even typically the result of neurological impairment, but I do think it would be a bit thickheaded to deny that it might not be the case in some patients.
In recent years, more attention is being paid to dopaminergic antidepressants, but I don't expect that any miracles are waiting just around the corner. Psychotropic medications are blunt instruments and dopamine agonists can show wildly different effects from one person to the next. There are multiple dopamine systems in the brain, so a drug that remedies depletion in one critical system might simultaneously overdose another critical system, leading to great variance in side-effect profiles. The same dopamine agonist that enhances learning in one patient can impair it in another. And then there is the infamous gambling side-effect. It has been reported that some patients who never gambled before behave like gaming addicts when they take anti-Parkinson's drugs, as if contingencies become so powerful that the patient is helplessly over-motivated by reward and punishment schedules.