Nicotine stimulant effect

Nicotine is the main psychoactive ingredient of tobacco and is responsible for the stimulant effects and abuse/ addiction that may result form tobacco use. Cigarette smoking rapidly (in about 3 sec ) delivers pulses of nicotine into the bloodstream. Its initial effects are caused by its activation of nicotinic acetylcholine (nACh) receptors. nACh receptors are ligand-gated ion-channels and pre- and postsynaptically located. Reinforcement depends on an intact mesolimbic dopamine system (VTA). nACh receptors on VTA dopamine neurons are normally activated by cholinergic innervation from the laterodorsal tegmental nucleus or the pedunculopontine nucleus. 

Mihailescu, S., Guzman-Marin, R. Drucker-Colin, R. (2001). Nicotine stimulation of dorsal raphe neurons effects on laterodorsal and pedunculopontine neurons. Eur. Neuropsychopharmacol. 11, 359-66. 

Newhouse PA, Potter A, Singh A (2004) Effects of nicotinic stimulation on cognitive performance. Curr Opin Pharmacol 4 36-46... 

Fig. 2 Effects of self-administered nicotine on dopamine overflow in the accumbal shell and core. Rats were trained to self-administer nicotine (0.03 mg kg per infusion). Microdialysis probes located in the accumbal shell and core were used to measure dopamine (DA) overflow during week 1 of training and in week 3 when the animals had acquired the response. Nicotine was available to the rats during the period indicated by the bar. The results are expressed as mean SEM, In the shell (left), nicotine stimulated DA overflow in both week 1 and week 3, the response in week 3 being higher (P < 0.05) than the response in week 1. In the core (right), DA overflow was only increased in week 3. Reproduced with permission from Lecca et al, (2006)...

Clarke PBS (1990) Dopaminergic mechanisms in the locomotor stimulant effects of nicotine, Biochem Pharmacol 40 1427-1432... 

Low doses of nicotine stimulate respiration through activation of chemoreceptors in the aortic arch and carotid bodies, while high doses directly stimulate the respiratory centers. In toxic doses, nicotine depresses respiration by inhibiting the respiratory centers in the brainstem and by a complex action at the receptors at the neuromuscular junction of the respiratory muscles. At these neuromuscular receptors, nicotine appears to occupy the receptors, and the end plate is depolarized. After this, the muscle accommodates and relaxes. These central and peripheral effects paralyze the respiratory muscles. 

Nicotine is a tertiary amine compound composed of a pyridine and a pyrrolidine ring. It binds selectively to acetylcholine receptors at the autonomic ganglia in the adrenal medulla at neuro-muscular junction and in the brain. It exerts a stimulating effect in the cortex and a reward effect via the pleasure system in the limbic system. 

Contrastingly, it was found that presynaptic histamine H3-receptor activation lowers the hypertensive effect evoked by nicotinic stimulation of sympathetic ganglia (Oudart et al., 1995), or by electrical stimulation of the spinal sympathetic nerves (Malinowska and Schlicker, 1991, Godlewski et al., 1997a). In spontaneously hypertensive rats, these receptors are probably activated by endogenous histamine, since thioperamide increases arterial pressure. Therefore, histamine H3-receptors appear to be operative in hypertension, where histamine could play a modulatory role in the control of sympathetic system hyperreactivity (Godlewski et al., 1997a). 

The third species of Duboisia, D. hopwoodi, contains little tropane alkaloid content, but produces mainly nicotine and related alkaloids, e.g. nornicotine (see page 313). Leaves of this plant were chewed by aborigines for their stimulating effects. 

Nicotinic acid undoubtedly provides the basic skeleton for some other alkaloids. Ricinine (Figure 6.35) is a 2-pyridone structure and contains a nitrile grouping, probably formed by dehydration of a nicotinamide derivative. This alkaloid is a toxic constituent of castor oil seeds (Ricinus communis Euphorbiaceae), though the toxicity of the seeds results mainly from the polypeptide ricin (see page 434). Arecoline (Figure 6.36) is found in Betel nuts (Areca catechu Palmae/Arecaceae) and is a tetrahydronicotinic acid derivative. Betel nuts are chewed in India and Asia for the stimulant effect of arecoline. 

Other drugs may increase the effects of dextroamphetamine. For example, bicarbonate and other alkalin-izing agents increase the amount of amphetamines absorbed in the digestive system. Thiazides (potassium-depleting diuretics) decrease the amount of amphetamines that leave the body in urine. Also, other central nervous system stimulants, such as cocaine and nicotine, can amplify the stimulating effects of dextroamphetamines. 

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. 

As mentioned in Part 2, there are drugs that can interfere with the inactivation of neurotransmitters. In that particular case the reversible cholinesterase inhibitor neostigmine was discussed within the context of treating myasthenia gravis. Excessive blockade of acetylcholinesterase at both muscarinic and nicotinic synapses results in a sustained excess of acetylcholine, which persistently activates the effector they innervate. Muscarinic stimulation results in excessive salivation, lacrimation, bronchiolar secretions, and bronchoconstriction. Nicotinic stimulation produces effects such as those described earlier for nicotine. 

Boye SM, Grant RJ, Clarke PB (2001) Disruption of dopaminergic neurotransmission in nucleus accumbens core inhibits the locomotor stimulant effects of nicotine and D-amphetamine in rats. Neuropharmacology 40(6) 792-8O5. 

Nicotine s CNS-stimulating effects, coupled with the frequent perception that it is sedating, arc powerfully reinforcing to humans. Nicotine remains a highly accessible drug in spite of the numerous taxes levied on its purchase over the years. In addition, although the number of social. settings where nicotine use is acceptable has decreased, there remain in the United States enclaves of. social support for its use. 

Nicotine s acute effects involve the CNS and ANS. It tends to have stimulant effects at lower doses but more depressant effects at higher doses. 

Areca catechu is a palm tree cultivated in Southeast Asia, India, and Africa. The nuts of this palm, often referred to as betel nuts, are chewed by more than 200 million people to produce a mildly stimulating effect. So, though not often seen in the United States, areca is one of the world s most popular drugs. Chewing areca or betel is a practice similar to chewing tobacco in the United States, and, like nicotine, the active chemical in areca, arecoline, affects the neurotransmitter acetylcholine. Users appear to develop a nicotine-like dependence on areca. Heavy use stains the mouth and lips red and damages the mouth and teeth, but users are often unable to quit chewing despite these problems (Spinella, 2001). 

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