Post-traumatic stress disorder (PSTD) is not a unitary disorder, but rather a syndrome, a clustering of propensities resulting from wide-ranging effects of stress hormones on the brain. So far we have looked at the effects of stress on gross physiognomy (in a tadpole, but it works on humans, too, as in Cushing’s disease), the upregulation of anxiety and depressive-like states, and effects on arousal, vigiliance, and concentration. In reading Ilona’s book, Moving a Nation to Care, I was struck both by the diversity of symptoms and how all of these symptoms are related to the consequences of chronic exposure to elevated corticosteroids (stress steroids). Indeed, so was Hench when he accepted his & Kendall’s Nobel prize for their successful clinical trials of cortisone (Kendall’s compound E) on rheumatoid arthritis; so much so, that he warned that corticoisteroids have wide-ranging side-effects, including Cushingoid redistributions of body fat, anxiety, depression, irritability, restlessness, euphoria, and even psychoses. Brilliant observation. Let’s us now turn our discussion of PTSD to the stress-associated "reward cluster" of symptoms.
From the Marlboro Man’s five-pack-a-day cigarette habit to alcohol abuse and excess drug-taking in many returning soldiers, to the strange desire to want to return to and relive the sources of stress, to sensation-seeking and impulsiveness seen in many returning soldiers and others suffering from post-traumatic stress disorder (PTSD), one has to ask why PTSD is associated with addiction-like outcomes.
First, I don’t want to give the impression that when veterans claim to abuse drugs in order to quiet their restless and troubled minds that they are not being truthful. That’s another story. My interest today is in the rewarding properties of stress, and how that occurs, and why life just isn’t the same back home.
From Ilona’s book:
"When you’re in combat, the adrenaline rush, it becomes fluid, you’re used to it all the time. Then when you come back, it’s not there anymore and you have to find to get back to how it was" --Jason Harvey:
Dopamine: Reward, Wanting, & Euphoria: The Natural Reward System
Above is a cartoon of the mesolimbic (mid-brain to limbic brain)/mesolimbic-prefrontal (mid-brain to prefrontal cortex) dopamine system originating in the ventral tegmental area (VTA) of the midbrain, and projecting to the nucleus accumbens and prefrontal cortex. This system has been most frequently and closely associated with reward, pleasure, and wanting. At one level of processes, it is associated with hardcore motivation, whether for food, sex, or aggression. At another level, it is associated with stamping in habits. If you block activity in this system, you take the wind out of an animal’s sails. It won’t run as much, or as fast, if at all. It won’t work hard to gain food or sex, or to escape or prevail in agonistic contests. If you make tasks progressively more difficult to gain reward, in order to find out where is an animal's "breakpoint," that ratio of work to reward at which an animal will simply give up, an animal without dopamine will give up much sooner than one with. It’s an extremely adaptive thing to WANT to achieve. A lion may have to chase quarry in hot pursuit on twenty different occasions before it finally gets food, and giving up is not adaptive. In fact, this system is designed so that the chase itself is rewarding and encouraging. You’ve seen how many times males strike out talking to females in a bar. It is pitiful, yet, even the smallest crumb of acknowledgement or acquiescence by a female can be hugely stimulating. The chase itself thrills, and is self-stimulating. The closer you get to actual reward, the more dopamine you pump, because pumping more dopamine means you are getting closer to the end goal. In this way, wanting can be its own reward.
Self-Stimulation and the Rush of Wanting:.
You’ve heard of experiments where animals have an electrode placed in the brain and can stimulate themselves by pressing a bar to receive current in the brain. That electrode is stimulating dopamine. When animals self-administer drugs, such as cocaine, amphetamine, or heroin, the drug is stimulating dopamine transmission. As you know, animals in these kinds of experiments can bar press for days at the expense of eating, having sex, or any number of other rewarding activities. Why go to the trouble of doing those other things, chasing quarry, going to the kitchen to make a sandwich, or chatting up females, when you are already directly stimulating the system that makes you think you are already on the right track? With that kind of direct stimulation, you are already so far down the road to success, it doesn’t make sense to back up and start from the beginning does it? Logically, yes, it does make sense, but motivationally, it is ludicrous. It feels so good to do a little blow. Got anymore? What? We're out already? We've only been doing this for three days straight! Thus you are trapped in a cycle of wanting. The stimulation itself makes you want to get a little closer. And that bar that you press to obtain more wanting is now your best-fucking friend, when just a little while ago, it meant absolutely nothing. Now, that bar is an incentive, an incentive with great meaning. It itself can reinforce other behaviors, whatever behaviors put you back in contact with that bar.
Dopamine & Time Perception: The Rush of Time
From Ilona’s book:
The feelings that Douglas Barber described—"coping with an everyday routine...a short fuse...on guard..." graphically illustrate one of the major problems that many veterans have in re-entering the regular world after serving in combat: that of replacing the adrenallized "war rush." In battle, things move at a rapid pace, as speed can mean the difference between life and death.
Harvey, who was kicked out of the army after being found with a loaded gun and ws later diagnosed with PTSD, drove his car at dhigh speeds and played paint ball to duplicate the feelings he had had in combat. "It might sound strange, but for me, when I was driving fast, it made me calm again," he recalled.
"From that tempo to civilian life, it’s incredibly slo-o-o-ow."
--Chris Bair
In addition to creating the euphoric rush, a central motive state of wanting, even craving, drugs associated with enhanced dopamine transmission also alter the perception of time. There is more to the "adrenaline rush" than just adrenaline. You can train a rat to judge intervals of time, say the duration of a tone, say, a 3 sec tone versus an 8 second tone, and then test them with tones of varying durations to see whether they say it’s the short tone or the long tone. They are very good at it. In a non-drugged rat, a 4 sec tone will be judged as "short," whereas a 7 sec tone will be judged as "long." A tone of intermediate duration will produce 50/50 behavior. If you train the rat with amphetamine, then test them "sober," they will start judging the 3 sec tone as "long," and the 8 sec tone as impossibly long. Conversely, if you train them sober, then test them under the influence of the amphetamine rush, they will now judge the 8 sec tone as "short" and the 3 sec tone as impossibly short. Regardless of whether it’s training or testing, under the influence of amphetamine (high dopamine efflux), time flies. Time flies in war. Time drags at home.
Stress Steroid Hormones as Reward.
As Hench implied in his Nobel address, stress steroids do not appear to have an intrinsic valence, elevations of steroid don’t necessarily feel either good or bad. Either outcome is possible. We know they can make you feel bad by stimulating the vital anxiety juice, CRF. And they probably make you feel good by stimulating dopamine. Like drugs of abuse or electrical stimulation of the brain, stress steroids will be self-administered by unstressed rats to the point of providing their brains with stress levels of steroid. Let's look at what stress steroids do to dopamine efflux in the nucleus accumbens, a primary target of mesolimbic dopamine (data adapted from Rouge-Pont et al, 1998).
In the above panel, rats were fasted for some number of hours, then allowed to eat where the arrow is shown at time zero. The rat's eating is coupled to drinking. The rats in orange drank normal water, and because these natural reinforcers stimulate dopamine, they show a gradual rise in dopamine efflux. The rats in blue had their water spiked with the stress hormone, corticosterone (compound B). Look at their dopamine efflux gush.
In the next panel, one group of rats (orange dots) had their adrenal glands that synthesize stress steroids removed, and they were replaced with constant, low concentration of steroid that cannot access the high affinity receptor stress receptor in brain. The other rats (blue dots) had sham operations and their adrenals were intact, so they could exhibit a proper stress response. At time zero they each received a tail pinch.
Notice how the animals capable of producing an adrenal stress response show much greater dopamine efflux than animals whose steroid levels are clamped at low levels that are insufficient to occupy central "stress" receptors.
Finally, to show that it was indeed the increase in the stress steroid concentrations, both groups had their adrenals removed, and were replaced with low steroid concentrations. Just before getting the tail pinch, one group received an additional booster injection (blue dots) to mimic the stress response, whereas the other group (orange dots) received a saline injection.
Again, it appears that increases in stress steroids amplify dopamine efflux, and presumably any subsequent effects of elevated dopamine on brain.
In the next diary, I will describe the combined effects of stress and drug use, because it is one helluva cocktail.