You may remember Highlights magazine from when you were a kid (or parent). Highlights has a feature where readers have to spot the differences between two similar pictures.
Dopamine gets a lot of press, and cocaine addiction research has generally focused more on dopamine. (What is “the molecule behind all our most sinful behaviors and secret cravings?â€) Norepinephrine is usually described more prosaically, as a hormone related to attention, stress and blood pressure regulation. Lowering norepinephrine levels does not stop animals from giving themselves a steady stream of cocaine, but it does inhibit their tendency to try to get it after a break or exposure to relapse triggers.
What is the difference between these two important brain communication chemicals, dopamine and norepinephrine? Look closely.
The answer is: just one oxygen atom. But it’s enough to mean http://www.magliettedacalcioit.com that the two neurotransmitters use different receptors and dominate different groups of neurons in the brain.
An area of medicine where that subtle difference is crucial is drug abuse. Geneticist David Weinshenker is an expert on the enzyme that converts dopamine into norepinephrine: dopamine beta-hydroxylase or DBH. He and his lab have been exploring whether medications that inhibit DBH could be used to help treat cocaine addiction.
DBH inhibitors are able to stave off relapse-like behavior in animals trained to give themselves cocaine. The National Institute on Drug Abuse began a multicenter clinical trial testing one such drug, nepicastat, in cocaine dependence this spring.
In a recent paper in the Journal of Pharmacology and Experimental Therapeutics, Weinshenker and postdoctoral fellow Daniel Manvich report on how DBH inhibitors act in terms of cocaine’s “discriminative stimulus.”
In these types of experiments, rats push levers to receive food pellets – the cocaine itself is not the reward. Instead, they have to be able to discriminate whether they have just received a cocaine injection and act accordingly.
The rats are supposed to push one lever after they receive an injection of cocaine and a different one after they receive saline. The rats are rewarded with food only if they push the appropriate levers, and they are trained until they push the right levers at a high enough accuracy. The test comes Cheap Jerseys when the rats are given a lower dose of cocaine that what they’ve been trained on. Normally, they can’t tell the difference between saline and a dose of cocaine that is five times weaker than what they’re used to.
Manvich and Weinshenker report two main results:
*Luckily when considering its potential use for treatment of addiction, nepicastat doesn’t by itself “feel like†cocaine; the rats don’t start pushing the cocaine-linked lever after they receive nepicastat.
*Under the influence of nepicastat, the rats are more sensitive to the effects of cocaine. This doesn’t say whether nepicastat makes cocaine feel more or less pleasant, only that the rats can discern the effects of smaller amounts of cocaine.
However, evidence has accumulated from both human and animal experiments that DBH inhibition may heighten the more unpleasant aspects of the “cocaine experience,” such as feeling anxious or paranoid. The authors note in their discussion:
We… propose that DBH inhibition may produce an unexpected therapeutic benefit in cocaine abusers by potentiating the aversive effects of cocaine during a relapse episode. Thus, in addition to evidence that treatment with DBH inhibitors reduces craving for cocaine and promotes abstinence by interfering with stress, cue, and drug triggers to precipitate relapse, their use may also include the added benefit of producing an aversive reaction after cocaine use that will further deter future drug intake.
 Weinshenker notes that DBH inhibitors are likely to act similarly with respect to amphetamines as well.
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