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Nicotine: sensitizes reward system? (opposite of other drugs of abuse)

~_Hiss_~

~_Hiss_~

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According to Wikipedia's article on nicotine,

Nicotine also sensitises brain reward systems...
Dopamine is one of the key neurotransmitters actively involved in the brain. Research shows that by increasing the levels of dopamine within the reward circuits in the brain, nicotine acts as a chemical with intense addictive qualities. In many studies it has been shown to be more addictive than cocaine and heroin, though chronic treatment has an opposite effect on reward thresholds[citation needed]. Like other physically addictive drugs, nicotine causes down-regulation of the production of dopamine and other stimulatory neurotransmitters as the brain attempts to compensate for artificial stimulation. In addition, the sensitivity of nicotinic acetylcholine receptors decreases. To compensate for this compensatory mechanism, the brain in turn upregulates the number of receptors, convoluting its regulatory effects with compensatory mechanisms meant to counteract other compensatory mechanisms. The net effect is an increase in reward pathway sensitivity, opposite of other drugs of abuse such as cocaine and heroin, which reduce reward pathway sensitivity.[18]
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I'm well aware of the possibility of made up stuff on there. Like that it is more addictive than heroin, what a joke. Being a dip addict myself i haven't noticed any increase in reward. maybe if i stopped? after the few days of lousy withdrawal.

Here is the cited source for this:

^ a b Kenny PJ, Markou A (Jun 2006). "Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity". Neuropsychopharmacology 31 (6): 1203–11. doi:10.1038/sj.npp.1300905. PMID 16192981. http://www.nature.com/npp/journal/v31/n6/full/1300905a.html. "However, these effects are an illusion brought about by Nicotine addiction. What appears to be relaxation, is merely the effect of ending the craving for Nicotine. The longer the periods between Nicotine intake, the greater the illusion of pleasure will be.".

It seems that maybe the increased sensitivity might just be for nicotine itself. Comments?
 
I posted an article here from SciAm or something like that a little less than a year ago that went over this sort of thing.

Ill see if I can find it. I'm sitting on the porch righ tnow to get wifi, and I'm freezing.
 
~_Hiss_~ said:
According to Wikipedia's article on nicotine,



I'm well aware of the possibility of made up stuff on there. Like that it is more addictive than heroin, what a joke. Being a dip addict myself i haven't noticed any increase in reward. maybe if i stopped? after the few days of lousy withdrawal.
Click to expand...

Meh it's all case... varies person to person. I don't find opiates addictive.. but I do get the feeling I could really go for some nicotine at the moment.
 
Opiates are very addicting, but I don't know if I believe this article considering its wikipedia...
 
I dont think the relevant point here is the degree to which opiates are addictive. Beside that addiction is a complex phenomenon with many neurochemical, social, behavioral, and market components playing a role. Personally I believe that comparative analysis of compounds to determine addictiveness is mostly bunk outside of a given specific drug class (IE DAM is more addictive than Morphine because of quicker BBB penetration). What I am trying to say is that comparing coke, heroin, and nicotine is not a fair comparison because of all the variables involved which can never be controlled for in practical real world usage.

But back to the original point of the discussion, just because it sensitizes reward pathways I do not believe that this means nicotine will necessarily make other dopaminergic drugs feel subjectively more pleasurable. It just means that you get a stronger reinforcing response from DA release. There is debate over what role DA release plays in pleasure period, check out a thread that hammilton was posting in recently about opiates and the role of DA. It may be the cause of addiction but probably not subjective pleasure. This is also supported by the fact that non-pleasurable alkaloids in opium will make animals dependent and seek redoses, for example thebaine.
 
This is also supported by the fact that non-pleasurable alkaloids in opium will make animals dependent and seek redoses, for example thebaine.
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Are we sure thebaine isn't pleasurable at all? Apomorphine is reinforcing in previously habituated meth-head mice, for instance. As a DA agonist, I don't doubt that it may be somewhat pleasurable so long as you're not puking your brains out.
 
^ I thought that the consensus from the thebaine thread started by nabollocks was that thebaine did not produce physical dependence. I think that mice still SA'd it under certain conditions, but I can't remember for certain if they did.
 
According to a study I read monkeys will self administer it and suffer severe withdrawals after ceasing use. What is pleasurable to a monkey I couldn't say as these animals enjoy throwing their own feces at each other but to my knowledge all the human bioassays report it as a bad experience.
 
Titre du document / Document title
Does nicotine affect D2 receptor upregulation?: A case-control study
Auteur(s) / Author(s)
SILVESTRI S. (1) ; NEGRETE J. C. (2) ; SEEMAN M. V. (1) ; SHAMMI C. M. (1) ; SEEMAN P. (3) ; RUSHLOW Walter (Commentateur) (4) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Centre for Addictions and Mental Health and Department of Psychiatry, University of Toronto, Toronto, Ont., CANADA
(2) Department of Psychiatry, McGill University Health Centre, Montreal, Quebec, CANADA
(3) Department of Pharmacology, University of Toronto, Toronto, Ont. N6A 5A5, CANADA
(4) Neuropsychiatry Research Group, Department of Psychiatry, the University of Western Ontario, London, Ont., CANADA
Résumé / Abstract
Objective: Nicotine has a powerful preventive effect on neuroleptic-induced dopamine D2 receptor upregulation in the rat. The aim of this human positron emission tomography (PET) study was to compare upregulation in a smoker and a non-smoker, both of whom had received haloperidol for the same duration of time. Method: Two subjects who had been treated for 16 years with a constant dose of haloperidol were scanned after temporary haloperidol withdrawal, using [11C]-raclopride. Results: The non-smoker, who had received a dose of 10 mg/day, showed a D2 upregulation of 98% and developed severe and persistent symptoms of tardive dyskinesia (TD) upon withdrawal. The chronic smoker, who had been treated with 40 mg/day, displayed a D2 upregulation of 71% and did not develop TD. Conclusion: These human observations agree with animal data which showed that nicotine can decrease neuroleptic-induced D2 receptor upregulation. This property of nicotine may play a protective role in movement disorders whose pathophysiology involves D2 receptor hypersensitivity.
Revue / Journal Title
Acta psychiatrica Scandinavica ISSN 0001-690X CODEN APYSA9
Source / Source
2004, vol. 109, no4, pp. 313-318 [6 page(s) (article)] (48 ref.)
Langue / Language
Anglais
Editeur / Publisher
Blackwell, Oxford, ROYAUME-UNI (1961) (Revue)
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There are also studies out there regarding an increase of glutamate receptor upregulation with nicotine use.
 
Could somebody breakdown what upregulation is versus downregulation? Is it more receptors versus less receptors or what?
 
downregulation is the reduction of voltage transmitted through the ion channels in response to neurotransmitters locking in and triggering receptors. upregulation is the obverse. the purpose of these processes is usually to prevent the signal strength hitting certain vital receptor types (glutamate, acetylcholine) down the line on a neuron's other dendrites where for example with glutamate the result is a massive increase in glucose metabolism which can result in neuron death from overheating... or something like that? or maybe it's spill-over effects from this and the result is an overload which is a major part of the aetiology of epilepsy at least.

also it acts as a brake on excessive neurotransmitter activity in general, as more release means more mao activity which increases oxide and superoxide production (O2-) which directly damages synapses and indeed the whole neuron. this aspect is believed to be the mechanism through which deprenyl extends lifespan (in rats at least) as the most critical, least numerous (i might be wrong on that point) and delicate synapses transmit dopamine and as we see in parkinson's disease leads to death. the damage from mao is an essential cost of neurotransmission because over time neurotransmitters degrade so some of it has to be decomposed periodically and a constant refreshing of the supply has to be done in order to maintain proper function.

however it's not just dopamine, as is becoming increasingly obvious to neuroscientists, dopamine is just one part of the complex system that governs the learning process and seeking/aversion behaviour. nicotine is a mao-a inhibitor similar to deprenyl in this respect, and thus increases the amount of dopamine neurotransmission without increasing the oxidative load from mao, as well as increasing serotonin activity (not sure what type or where specifically) and in fact the serotonin most probably plays as big a role as the dopamine in the 'feel good' (probably more likely pressure-release cycle similar to used in animal training) effect that helps reinforce the behaviour.

having said this, and as a former smoker, it is my opinion that a buttload of horseshit that is believed about the process of nicotine addiction and withdrawal, the whole 'rebel' defiant cool factor, even the language used to describe withdrawing 'quitting' are at least as important in maintaining addiction as the neurochemical alterations caused by nicotine. the tobacco companies (many of them are major interests or owners of arrays of other companies, eg phillip morris owns kraft) and the government who gets a huge cut of the trade in tobacco has no genuine interest in people really stopping smoking, i mean, how exactly do they justify it costing more for the nonsensical nicotine replacement therapy? or is that because people might then switch to using patches and get all the benefits of nicotine and none of the health problems caused by smoking.

in actual fact the only physical withdrawal effects of nicotine are a reduction in the ability to concentrate, an ability that is enhanced by both neurochemical changes described above plus an acetylcholine activity increase that improves memory function, and this effect is only temporary and lasts at most a week, and is, as studies have shown, a marked improvement (the military studied it and found that it improved performance) is engendered to users of nicotine, however just to end any nonsense on that point there's loads of drugs that specifically enhance memory and cognition well beyond what nicotine can do and we all know how evil and wrong it is to take drugs that affect the brain specifically and get a benefit.
 
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