The Needle and the Damage Done

I got a sickness
Sweet as a love note
I got a headache
Like a pillow

Much of 20th century experimental psychology was dominated by the behaviorist school of B.F. Skinner. They saw essentially all behavior as a product of a life history of rewarded and punished actions. At the time, scientists were very interested in understanding the brain circuits that process rewards. Olds and Milner made a crucial breakthrough by discovering a technique known as 'intracranial self stimulation' or ICSS. This discovery emerged from experiments that involved implanting a stimulating electrode into a rat's brain and zapping it every time the rat went to a specific location. They found that the rat started spending most of its time at that location. So then they decided to hook the stimulator to a lever that they rat could press itself and the results were terrifying.  Pretty quickly the rat figures this out and subsequently it doesn't give a shit about anything but pressing the lever. It will do almost anything for free access to the lever, including enduring painful electric shocks and forgoing food. Yes that's right. The rat will sooner literally starve to death than stop pressing the lever.



This experiment is effective with stimulation of a number of brain targets, but one of the most effective and best studied is the mesolimbic pathway originating in the ventral tegmental area or VTA. You get one guess which neurotransmitter is released by the VTA.

*********

One of the main topics of my parky meeting was something we don't often discuss, particularly with those who aren't members of our club: the effects of dopamine replacement therapy on impulse control. I volunteered to lead this discussion because reward processing and motivated behavior are of considerable scientific interest to me, but I was unprepared for the terrifying window it would give me into the personal devastation that can occur with certain P drugs.

Most P symptoms are believed to result from depletion of the neurotransmitter dopamine. Strategies for fixing this fall into two broad categories. One approach is to feed your dopamine cells with L-DOPA to help them manufacture more dopamine. Another strategy is to enhance the effects of the dopamine you still have with something called an agonist.

Most people find taking agonists helpful. I do. However, they sometimes have some weird side effects that are almost certainly related to the rats and the lever. When I say 'sometimes' that might be 14% of the time if you believe the drug companies or 100% if you believe some parkys. It seems clear to me that the number is somewhere in between. Where exactly depends on where you draw the line between harmful and harmless. I can certainly be compulsive/impulsive. Anyone who knows me well and/or follows me on Facebook surely knows what I mean. Fortunately, my destructor has chosen a relatively benign shape and amplitude.

Other people aren't so lucky. For one thing, the blunt reality is that dopamine replacement drugs are drugs of abuse. Remarkably, I actually never thought of it in this framework, but people literally pop these pills (or even take them as directed) and pursue darker, more dangerous obsessions. Sex, shopping, gambling, risky investment, shoplifting whatever. In extreme cases, people no longer give a shit about anything but 'pressing the lever'. I heard a lot of stories about what these drugs have done to people and it shook me up.

L-DOPA fixed me, alright!