Thursday, September 24, 2015

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!


  1. "The Needle and the Damage Done" is a song about drug abuse by Neil Young. The lyrics are from the song "L-DOPA" by Big Black.

  2. In every life a little glib must fall. If agonists juice 14-100% of us into compulsive behaviors, that number is markedly higher when combined with Levodopa therapy.

    Because if you don't laugh you'll cry, here's what Ricky Martin meant to sing in his hit originally titled 'Livin' the Levodopa.' ('Livin' the Ropinirole' just didn't scan. You'll never again hear it as you did before.):

    She's into superstitions black cats and voodoo dolls.
    I feel a premonition that girl's gonna make me fall.
    She's into new sensations new kicks in the candle light.
    She's got a new addiction for every day and night.

    She'll make you take your clothes off and go dancing in the rain.
    She'll make you live her crazy life but she'll take away your pain
    like a bullet to your brain. Come On!

    Upside, inside out she's livin the levodopa
    She'll push and pull you down, livin the levodopa
    Her lips are devil red and her skin's the color mocha
    She will wear you out livin the levodopa Come On!
    Livin the levodopa, Come on!
    She's livin the levodopa.

    Woke up in New York City in a funky cheap hotel
    She took my heart and she took my money
    she must've slipped me a sleeping pill
    She never drinks the water and makes you order French Champagne
    Once you've had a taste of her you'll never be the same
    Yeah, she'll make you go insane.

    She'll make you take your clothes off and go dancing in the rain.
    She'll make you live her crazy life
    but she'll take away your pain like a bullet to your brain. Come On!