Nicotine brain levels dependence

Inhaled nicotine is efficiently delivered to the brain (see chapter by Benowitz, this volume) where it selectively interacts with its central targets, the neuronal nicotinic acetylcholine receptors (nAChRs). The multiple subtypes of uAChR (see chapter by Collins et al, this volume) all bind nicotine but with different affinities, depending on the subunit composition of the uAChR. Binding may result in activation or desensitisation of uAChRs, reflecting the temporal characteristics of nicotine dehvery and local concentration of nicotine. Another level of complexity of the actions of nicotine reflects the widespread and non-uniform distribution of uAChR subtypes within the brain, such that nicotine can influence many centrally regulated functions in addition to the reward systems. In this chapter, we address the consequences of nicotine interactions with nAChRs at the molecular, cellular and anatomical levels. We critically evaluate experimental approaches, with respect to their relevance to human smoking, and contrast the acute and chronic effects of nicotine. 

Nicotine binds selectively to the nicotinic receptors that are present in the adrenal medulla, brain, autonomic ganglia, and neuromuscular junctions. It causes the release of several neurotransmitters and hormones such as acetylcholine, norepinephrine, dopamine, serotonin, arginine vasopressin, j3-endorphin, adrenocorticotropic hormone, and cortisol (187). This neuro-regulatory effect of nicotine is dose-dependent and occurs as plasma nicotine level rises when tobacco is smoked. The neurotransmitters released in the brain medi-... 

Another efficient modality for smoking cessation is bupropion.The antidepressant activity of bupropion is achieved through its effects on the levels of dopamine and norepinephrine in the brain (the effects of bupropion are mediated by blocking the reuptake of both dopamine and norepinephrine ). These effects are thought to underlie its positive results in clinical trials of patients with tobacco dependence (bupropion about doubles long-term abstinence rates compared with placebo). Increased brain levels of dopamine and norepinephrine would be expected to counteract the deficiency of these neurotransmitters during nicotine withdrawal and thereby aid in smoking cessation. 

Other claims for megadoses of nicotinic acid or nicotinamide, such as the claim that abnormalities associated with schizophrenia, Down s syndrome, hyperactivity in children, etc. can be reduced, have so far failed to win general acceptance. Clearly niacin deficiency or dependency can exacerbate some types of mental illness such as depression or dementia. There have been a number of attempts to treat depression with tryptophan or niacin, or both, on the basis that the correction of depressed brain levels of serotonin would be advantageous. However, these have met with only limited success. Schizophrenics have been treated with nicotinic acid on the basis that their synthesis of NAD is impaired in some parts of the brain, and that the formation of hallucinogenic substances such as methylated indoles may be controlled. 

Rosecrans JA, Chance WT (1978) The discriminative stimulus properties of n- and m-cholinergic receptor stimulants. In Ho BT, Richards DW III, Chute DL (eds) Drug discrimination and state dependent learning. Academic, New York, pp 119-130 Rosecrans JA, Schechter MD (1972) Brain area nicotine levels in male and female rats of two strains. Arch Int de Pharmacodynamic et de Therapie 196 46-54 Rosecrans JA, Kallman MJ, Glennon RA (1978) The nicotine cue an overview. In Colpaert EC, Rosecrans JA (eds) Stimulus properties of drugs ten years of progress. Elsevier-North Holland, Amsterdam, pp 69-81... 

Dopaminergic activity. Smoke was administered intranasally to mice for 20 minutes twice daily for 3 days before methamphet-amine treatment. The treatment significantly attenuated the neurotoxicity as judged by a lesser depletion of dopamine, dihydrophenylacetic acid, and homovanillic acid. The lesser effect of methamphetamine on the content of serotonin level was unaltered by prior inhalation of smoke h Tobacco glycoside, administered to mice, increased behavior via dopamine 2 neuronal activity but not dopamine 1 activity in a dose-dependent manner. The results indicated that smoking can affect the human brain function via not only the nicotinic cholinergic neuron but also the dopamine 2 neuron . 

Mitochondrial ATPase inhibition. Smoke extract, in the mouse brain mitochondria culture in the presence or absence of vitamin C for 60 minutes, inhibited mitochondrial ATPase and cytochrome C oxidase activities in a dose-dependent manner. The effect of extract on mitochondria swelling response to calcium stimulation was dependent on calcium concentrations. The extract treatment induced mitochondrial inner membrane damage and vacuolization of the matrix, whereas the outer mitochondrial membrane was preserved. Nicotine produced no significant damage . Mitogenic activity. Water extract of the dried leaf, administered to mice at a concentration of 0.05%, was active on lymphocytes from mesenteric lymph node and lymphocytes B and T. Intracellular Ca level was unchanged. The extract was active on... 

Although nicotine is a stimulant, it may induce muscle relaxation, depending on the user s physical state. It has also been shown to decrease one s appetite, speed up metabolism, and increase levels of dopamine, a mood-altering chemical in the brain that induces feelings of pleasure. Low levels of dopamine play a role in the development of Parkinson s disease. Research has shown that smokers, with higher levels of dopamine, have a reduced risk of the disease. Women who are pregnant are advised not to use any product containing nicotine. Nicotine in any form is harmful to an unborn child. It rapidly crosses the placenta and enters the fetus s body. 

Alcohol,psychostimulants (e.g., cocaine and methamphetamine), nicotine, and opiates, increase dopamine levels in the brain. The larger amount of dopamine give rises to feelings of pleasure, and is responsible for craving and drug dependence. 

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