Tuesday, 29 May 2007

pharmacology - How do Benzodiazepines induce Rewarding (Euphoric) effects?

Okay, I read the question wrong.



Benzodiazepines do not bind to GABAA receptors universally. Thus the presumption that it inhibits the mesolimbic dopamine pathway may be wrong. They may not interact directly with said pathway at all.



Many subtypes for the GABAA receptor exist. The receptor consists of 5 subunits. The following subunits are known to exist: α1-6, β1-3 and γ1-3. The most common combination has two α, two β and one γ. You find ones with distinct compositions at distinct locations in the brain. All have two bindingsites for GABA, but only a subset has an additional binding site for benzodiazepines.



The benzodiazepine binding site is at the interface of an α and a γ subunit, so receptors without this structure will show no affinity for benzodiazepines. Additionally the α subunit must contain a histidine residue, which is only true for α1, α2, α3 and α5. That is paraphrased from wikipedia, where you can find the sources as well.



I still think you need to consider the idea that benzodiazepines may not interact directly with the dopaminergic reward pathway, like opiates and cocaine does. I attribute the euphoria to be an indirect effect, resulting from the muscle relaxation (which will feel like you had a good massage), and the calmness of the mind.

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