Brain nicotinic system

Kenny PJ, Markou A (2005) Conditioned nicotine withdrawal profoundly decreases the activity of brain reward systems. J Neurosci 25 6208-6212... 

Henningfield JE, London ED, Jaffe JH (1987) Nicotine reward studies of abuse Uability and physical dependence potential. In Engel J, Orleand L (eds) Brain reward systems and abuse. Raven, New York, pp 147-164... 

In spite of the smaller ratio of nicotinic to muscarinic receptors in the brain, nicotine and lobeline (Figure 7-3) have important effects on the brainstem and cortex. The mild alerting action of nicotine absorbed from inhaled tobacco smoke is the best-known of these effects. In larger concentrations, nicotine induces tremor, emesis, and stimulation of the respiratory center. At still higher levels, nicotine causes convulsions, which may terminate in fatal coma. The lethal effects on the central nervous system and the fact that nicotine is readily absorbed form the basis for the use of nicotine as an insecticide. Dimethylphenylpiperazinium (DMPP), a synthetic nicotinic stimulant used in research is relatively free of these central effects because it does not cross the blood-brain barrier. 

Like most alkaloids, nicotine exerts its effects at receptors for chemicals that transmit nerve impulses. Specifically, nicotine acts at the nicotinic receptor class for the transmitter acetylcholine (the other class of acetylcholine receptor is the muscarinic, also named for a compound—a mushroom derivative— that triggers only receptors of that class). Outside the brain, nicotinic receptors are found primarily in the sympathetic nervons system, while muscarinic receptors are found in the parasympathetic nervous system. Thus, nicotine use triggers sympathetic nervous system effects throughout the body. 

Bupropion appears to reduce nicotine withdrawal symptoms and may simulate the actions of nicotine on the brain reward system. The most common side-effects related to bupropion are insomnia (30-45% at a dose of 300 mg/day) and dry mouth. Other commonly reported adverse events include hypertension, headache, and nausea. Seizures are a known risk associated with the use of somewhat higher doses compared with other antidepressants (0.1-0.4%), especially for the immediate-release form of the drug and when given at dosages of 450 mg/day or higher. Bupropion, unlike the TCAs, is virtually free of adverse cardiovascular effects, which makes it quite attractive for specific populations. 

Kenny PJ, Markou A. Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity. Neuropsychopharmacology 2006 31 1203-1211. 

Abused drugs, including alcohol, opiates, cannabinoids, and psychostimulants, such as nicotine, activate the mesolimbic dopaminergic brain reward systems and increase dopamine levels in the nucleus accumbens. Specific CBl receptors modulate the... 

Lthanol (or alcohol) is a two-carbon molecule that, in contrast to many other drugs of abuse, such as opioids, cocaine, and nicotine, does not bind to specific brain receptors. Nonetheless, alcohol affects a variety of neurotransmitter systems, including virtually all of the major systems that have been associated with psychiatric symptoms (Kranzier 1995). Alcohol affects these neurotransmitter systems indirectly by modifying the composition and functioning of... 

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

Corrigall, W.A., Coen, K.M., Adamson, K.L. Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Res. 653 278, 1994. 

The pleasure derived from using tobacco is linked to the stimulation of dopamine-dependent neurotransmitter pathways in the brain, particularly in the meso-limbic system. The precise nature of this link remains controversial, but many of the neurophysiological processes underlying nicotine addiction are common to other addictive drugs with diverse pharmacological actions such as opiates, cannabis, alcohol and cocaine. 

Nicotine is responsible for the highly addictive properties of tobacco products. Addiction occurs in 30% of those who experiment with tobacco products, and more than 80% of those who attempt to quit smoking will relapse within a year. Withdrawal from nicotine produces a syndrome characterized by nicotine craving as well as dysphoria, anxiety, irritability, restlessness and increased appetite. It is treated with nicotine replacement therapies, such as nicotine gum and patches, and/or with buproprion, a drug that is classified as an antidepressant but has multiple and complex effects in brain. Buproprion reduces craving in some smokers. Nicotine addiction has been reviewed recently at cellular and systems levels [38-41]. 

Indirect mechanisms Nicotine has indirect effects on monoamine systems. A considerable amount of research has examined the relationships between nicotine and dopamine activity in the brain, in light of dopamine s role in reinforcement and nicotine s addictive properties. Nicotine increases dopamine turnover in the striatum and cerebral cortex (Clarke and Reuben 1996 Tani et al. 1997 Nanri et al. 1998). It also increases burst activity in dopamine neurons of the ventral tegmental area (VTA), a primary source of dopamine to the forebrain (Nisell et al. 1995 Fisher et al. 1998). Such a firing pattern in the VTA is associated with processes of reinforcement, learning, and cognitive activity. Nicotine actions on dopaminergic neurons occur at both somatodendritic sites and synaptic terminals. Further, both systemic nicotine and direct administration into the VTA increase dopamine release in the nucleus ac-... 

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