intellectual vanities… about close to everything

The Brain And The Nicotine

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Three specific regions of the brain are known to be involved when the smokers craved cigarettes versus when they did not.

One region that lights up, called the thalamus, is considered to be the key relay point for sensory information flowing into the brain. Some of the symptoms of withdrawal among people trying to quit stem from the inability to focus thoughts and the feeling of being overwhelmed, and could thus be explained by changes in this region, according to the researchers. The researchers found that changes in this region were most dramatic among those who said they smoked to calm down when under stress.

smokerbrain.jpg

Another region that lights up is a part of the pleasure system of the brain. Changes in this region, called the striatum, were most notable in people who smoked to satisfy craving and for pleasurable relaxation, the researchers said.

A third region that lights up, called the anterior cingulate cortex, is vital to cognitive functions such as conflict, self regulation, decision making and emotion. People whose brain scans showed the most differences in this region also reported that they smoked to manage their weight.

Researchers from the Institut Pasteur associated with the CNRS, collaborating with scientists from the Karolinksa Institute (Stockholm) and the University of Bordeaux 1, have analysed the subtle balance between various types of nicotinic receptors in the brain during chronic exposure to nicotine. Their research, just published in PNAS, could make it possible to guide the development of more specific therapeutic molecules for smoking cessation, as well as for some neurological pathologies, such as Alzheimer’s Disease and autism, or psychiatric conditions like schizophrenia.

Nicotine is the principal substance in tobacco involved in addiction, in particular through the changes it causes in the reward system that naturally manages our desires, our pleasures, and our emotions. It acts by binding to nicotinic acetylcholine receptors. These receptors result from the assembly of five subunits; as there are nine different subunits, the receptors, as a consequence, possess a wide

variety of pharmacological properties. However, all are activated by the endogenous neurotransmitter acetylcholine, as well as by nicotine. These different types of receptors could therefore have distinct physiological functions, and represent specific pharmacological targets. Hence the importance of studying their respective roles.

This kind of analysis has just been achieved in a study led by Philippe Faure and Sylvie Granon, in the Integrative Neurobiology of Cholinergic Systems Unit of the Institut Pasteur, associated with the CNRS. Last year, these researchers deciphered the molecular basis for activation of our reward system during an acute injection of nicotine. They demonstrated the major role of one subunit of the nicotinic receptor, called beta-2, in this activation, and suggested the intervention of a second type of subunit, alpha-7.

In the present study, the researchers analysed the role of these receptors during chronic exposure to nicotine. Over several weeks, they administered doses of nicotine to mice allowing them to obtain concentrations of nicotine in the plasma similar to those found in a smoker, and sufficient to trigger a withdrawal syndrome.

By comparing “control” mice and mice genetically lacking the ß2 receptor, they were able to demonstrate that chronic exposure to nicotine modified the equilibrium between two contrasting processes, orchestrated by the beta-2 and alpha-7 receptors. The beta-2 receptors, after a sufficiently long period of exposure, undergo a long-term inactivation and desensitisation. This effect is counterbalanced by an adaptation of the neural circuits that depend on alpha-7. This is especially obvious in mice deficient in beta-2 subunits, for which the behavioural defects linked to the reward system are offset by the chronic exposure to nicotine. This compensation does not appear if the alpha-7 receptors are blocked.

Therefore, in the light of this study, it seems necessary to take into account these two types of receptors in order to develop molecules that would aid in ending tobacco addiction.

In addition, the authors emphasise that there are pathologies that involve the nicotinic receptors, among other biochemical changes. “In particular, this is the case with schizophrenia”, explains Faure. “The individuals treated for this disease smoke significantly more than the standard population, and some authors think that this would be a form of self-medication. This phenomenon could be due to the action of a compensatory mechanism linked to the alpha-7 receptors”. Other disorders, such as Alzheimer’s, the hyperactivity syndrome Attention Deficit Hyperactivity Disorder (ADHD), or autism, also appear to affect various types of nicotinic receptors.

“These results offer new avenues for developing and fine-tuning ‘nicotine-like’ agents for the treatment of certain neurological and psychiatric pathologies”, the authors conclude.

Proc Natl Acad Sci U S A. 2007 May 8;104(19):8155-60. Epub 2007 Apr 30.

Long-term effects of chronic nicotine exposure on brain nicotinic receptors.

* Besson M, * Granon S, *Mameli-Engvall M, * Cloez-Tayarani I,

* Maubourguet N, * Cormier A, * Cazala P, * David V,

* Changeux I.P., * Faure P.

“Recepteurs et Cognition,” Centre National de la Recherche Scientifique Unite de Recherche Associee 2182, “Unite de Neurobiologie Integrative des Systemes Cholinergiques,” Institut Pasteur, 75724 Paris, France.

Chronic nicotine exposure results in long-term homeostatic regulation of nicotinic acetylcholine receptors (nAChRs) that play a key role in the adaptative cellular processes leading to addiction. However, the relative contribution of the different nAChR subunits in this process is unclear. Using genetically modified mice and pharmacological manipulations, we provide behavioral, electrophysiological, and pharmacological evidence for a long-term mechanism by which chronic nicotine triggers opposing processes differentially mediated by beta2*- vs. alpha7*nAChRs. These data offer previously undescribed insights into the understanding of nicotine addiction and the treatment of several human pathologies by nicotine-like agents chronically acting on beta2*- or alpha7*nAChRs.

PMID: 17470777 [PubMed – in process]

see also:

smoking is a thing in the head…

Written by huehueteotl

May 20, 2007 at 2:08 pm

Posted in Arts, Science

2 Responses

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  1. Nicotine is a thing of the past for me… I was a can/day dipper for 16+ years, but I quit using the resources at http://www.killthecan.org/

    iuchewie

    May 21, 2007 at 6:53 pm


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