Why Levodopa & Bromocriptine Aren't Addictive

[Revenged]

I am well aware that high dopamine release causes addiction because it activates the reward centres in the brain...

Like with heroin, opioids causes dopamine release (via the disinhibition of GABA) and that causes activation of reward centres in the brain... You get addiction...

With amphetamines it is the same story... They cause dopamine release and they cause addiction...

But I am a bit confused about some of the drugs... I was learning about Parkinsons disease medication today and got a bit confused...

Levodopa - it is the precursor of dopamine and it is used in order to treat parkinson's disease... It travels through the blood brain barrier, where it is decarboxylated to form dopamine - and yet this increase in dopamine levels in the brain but it is not addictive...

Bromocriptine is a dopamine receptor agonist... It is given when levodopa is no longer effective... Since it activates the same receptors are dopamine - surely this would make it addictive?...

But levodopa and bromocriptine don't seem to be addictive as far as i know... so anyway, does anyone know why they aren't addictive?

 

[Moonbear]

There are many dopaminergic cell groups, and each of those has numerous projections to other brain areas. So, it depends on which of those cell groups is being affected. It's also a bit oversimplified to boil all of drug addiction down to only dopamine. Addiction isn't just the activation of the dopaminergic pathways (those pathways are activated when you don't become addicted as well). Addiction is more likely related to neural plasticity...physical changes in the synaptic contacts formed between different cell groups.

Here are some references to help you out:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6SYP-477799M-8&_coverDate=12%2F02%2F2002&_alid=521976559&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4840&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=117478fb586c6e32196911572f09a88e

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0C-4DBC9GS-5&_coverDate=12%2F31%2F2004&_alid=521977228&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4859&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5ed837dcd2586e1f8977c06a59a996be

Also, with regard to bromocriptine, and other receptor agonists, keep in mind that there are a number of dopamine receptor subtypes, so not all agonists/antagonists act on the same receptors. Bromocriptine is primarily a D2 receptor agonist. The process of drug addiction more likely includes D1 and D3 receptors.

In Parkinson's disease, levodopa is used to attempt to restore normal dopamine function, not to increase dopamine to elevated levels. There are some case studies reporting addiction to levodopa. As an example:

Tack E, De Cuypere G, Jannes C, Remouchamps A. Levodopa addiction. A case study. Acta Psychiatr Scand. 1988 Sep;78(3):356-60.

Abstract:

A case is presented of a young woman with a serious addiction to levodopa who over the years developed an extrapyramidal syndrome and chronic paranoid psychotic behaviour. The possible pathophysiological mechanism is discussed.

http://www.ncbi.nlm.nih.gov/entrez/...t_uids=2973725&query_hl=5&itool=pubmed_DocSum

 

[Revenged]

Ok... Thanks for that help...

I understand now that levodopa increases dopamine stores in neurones and that dopamine is only released when neurones are stimulated... I thought before that it just increased the dopamine levels... This would explain why levodopa is no longer effective when all the nerones running from the substantia nigra to the striatum die in late stage Parkinsons...

 

[wuliheron]

I agree, it is much more complex than any single neural transmitter. Cocain addiction, for example, has also been associated with the same part of the brain responsible for monogamous behavior. At any rate, eighty percent of all people with mental illness suffer from substance abuse at some point in their lives, and addictive personality disorder is usually an inherited condition.

www.na.org