Neurochemical pathway relating to addiction?

[Chainer]

Hey all,

quick question... was going through some research logs on cocaine addiction in rats and ran across a few things, but I figured I'd start light to see if I can even garnish an answer.

What neurochemical pathway is critical to establishing drug addiction? It's the limbic system, no? If so, is the normal function of the limbic system simply dopamine delivery, or am I completely off?

If it is, could the partial destruction of the limbic system mean partial destruction of neurochemical urges / addiction in a major sector of the brain? I was reading about how 6-hydroxydopamine can completely destroy certain short-term memory receptors in the hippocampus and was theorizing that perhaps this is a dangerous yet possible way to eliminate some neuron flaring that has to do with addiction cue-induced cocaine cravings. The biggest side effect I could think of would be dopamine regulation would have to be closely monitored in rats to see if it could ever re-establish itself back to a normal production rate, or if the limbic system could heal at all.

 

[qwe]

a lot of your questions i'll let someone familiar with neuro research handle

If it is, could the partial destruction of the limbic system mean partial destruction of neurochemical urges / addiction in a major sector of the brain?

The limbic system is also tightly connected to the prefrontal cortex. Some scientists contend that this connection is related to the pleasure obtained from solving problems. To cure severe emotional disorders, this connection was sometimes surgically severed, a procedure of psychosurgery, called a prefrontal lobotomy (this is actually a misnomer). Patients who underwent this procedure often became passive and lacked all motivation.

mess with your drug addiction and you mess with who you are. we can't scoop out the part of the brain that likes mcdonalds, sex, or drugs, without "amputating the soul"

If so, is the normal function of the limbic system simply dopamine delivery

brain systems are complex and many kinds neurotransmitters and neurotransmission are involved. dopamine is a central aspect to the limbic system, though, yes. some research i've read suggests that dopamine may mediate "craving/wanting" while endorphins may be closer to the "end of the neural pathway" for "pleasure". talking about this stuff in such an abstract manner can really obscure relevant complexities, though

 

[Chainer]

Thanks QWE - that does help me out a bit. I've been doing a lot of research into the limbic system and I am slightly familiar with with the primary aspects of it (hippocampus, amygdala, anterior thalamic nuclei, limbic cortex). I'm actually really interested in the promising aspects of 6-hydroxydopamine and how it can down-regulate dopamine, rather massively. I find it odd how we still have not found out so much about cocaine addiction when we know a relatively large amount about the limbic system.

I know it's a complex answer, so I wasn't expecting an overly simple answer to my question - in fact, the more info the better! I have a few journals that have stricken my interest and I was hoping the wizards here at ADD could help me out in a timely fashion - I'm interested in doing a paper on this subject for my neuroscience major requirements.

again, thanks for the fast response - I kinda have to choose my topic soon and this is really tugging at me. I should have done more background reading in other journals and in wiki, but I know there are TONS of BLers here who can summarize answers to those questions in an understandable manner. ya QWE.

edit: prefrontal lobotomy sounds about as dangerous as occular lobotomy, ie: not safe and rather stupid. I know it's been done in the early 30s, and still in lab rats, but I'm wondering what effect that would have in general on dopamine or if that would simply generate massive depression in humans. Either way, that's slightly off topic. I'm more interested in the primary function of the neurochemical pathways involved in addiction.

 

[fastandbulbous]

I've only got hazy memories of lectures on the structure & function of the brain (& I'm rather intoxicated at the moment!), but I think it's the nucleus accumbens that all the hoo-hah surrounding drugs, compulsive behaviour & the reward system is situated

 

[Runera46]

Addiction is a very interesting demon indeed!

The reward circuit is at the core of addiction. Although there are many views on addiction most involve the insula, amygdala and hippocampus. I'll have a dig through some good papers I have on addiction when I get a chance. Should help

*edit: As far as structural changes go. In the literature there are accounts of heavily addicted smokers sustaining damage to the insula and completely losing the addiction.

 

[Sturnam]

As others have mentioned, the reward pathway is critical for addiction, and it includes more than the structures in the limbic system. Briefly, this includes the ventral tegmental area, nucleus accumbens, striatum, and medial prefrontal cortex as the major players.

For a general mechanism, an addictive drug excites dopamine neurons in the VTA, which increase dopamine levels in the NA and striatum. I suppose if you lesioned the VTA or nucleus accumbens, you might be able to eliminate addiction, but you'd also be eliminating the pathway for natural reward.

 

[MeDieViL]

Glutamate plays a major role, especially in the development of tolerance, glutamate hyperactivity also occurs in many withdrawal states.

 

[Chainer]

Thanks guys! The info has helped me dig further and get a general better grasp of everything.

Currently reading about how after damaging the mesolimbic system and dopamine production with use of 6-hydroxydomaine, of rats addicted to amps, they will stop self administering due to low reward in the straitum.

It's funny how some journal logs can be so easy to read through for someone with a mediocre grasp on neurobiology, and some are far to advanced to read past the second sentence.

It's now my understanding that the mesolimbic dopamine dystm originates in the ventral tegmental area of the midbrain, which projects to the nucleaus accumbens. The amygdala and hippocampus and medial prefrontal coretext then sends exitatory projections to the nucleaus accumbens. Leaves me pondering the grande scheme of the limbic system - it seems BUILT to accept addiction over time... I mean, given the fact that many natural stimuli can act as dopamine cues, it leaves our brains quiet open to addiction... with almost *no* defense mechanisms against it beside rationalization from our society.

What's the main point of the limbic system anyway? It seems to act as a stimulus-response reward center more than anything, but is that for learning purposes (ie: don't touch hot stove, go have sex), or is it to enable easy addiction? Basically it is my understand that if we can limit our reward system in the brain, we can help reduce drug-cued tendencies by selectively attacking D2 receptors.

Hell, that opens a new topic all together, that some of us are pre-wired to become addicts based simply on our drug metabolism in our mesolimbic system.

 

[Chainer]

Are there drugs out there that act as uptake activators, such as a reverse of an SSRI, but towards dopamine or gluatmine? Selective Dopamine Uptake pills sound possible! SDU doesn't ring quiet like SSRI, but oh well. It seems a lot more safe and effective than lobotomy or neurotoxic injections to the reward center of the brain. It seems to me like such drugs could prevent use of nearly all narcotics by regulating how much dopamine or glutamine can remain in the synaptic cleft, instead sucking the chemicals back up to the presynapse where calcium and sodium will destroy them.

 

[melange]

or you could just use something like reserpine which depletes monoamines

 

[Chainer]

duh - forgot that a protein can effect the reuptake of catecholamines and tryptamines into the presynaptic terminal.

Isn't reserpine typically used for high blood pressure, or can it be altered/prescribed off-label for narcotic management?

Either way, major tangent. I still have the question: What is the original purpose of the pathways that involve addiction? Is it simply dopamine/glutamine/serotonin release in order to provide us with positive reinforcement for things like runners high or even sexual drive (reproduction)? Or is there something else that the mesolimbic and mesocortical pathways provide us with other than reward released chemicals?

edit: I found a journal that stated the mesolimbic system also influences learning, as learning can impact future reward and associations to rewards which will release dopamine.

I think I've got most of the answers I set out to look for. Funny how studying neurology can make you feel simultaneously intelligent and retarded, though I have a feeling many people in this major/field feel this way. If I missed anything, please feel free to add or correct me.