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Summary 2
The Effects of Bupropion Upon Nicotine Addiction
In developed countries, smoking is the largest cause of preventable deaths. Worldwide numbers of smokers are increasing, and though seventy percent of adult smokers report they wish to quit, only a tiny proportion of their number actually do. Dopamine overflow in the nucleus accumbens and activation of nicotinic acylcholine receptors within the ventral tegmental area (VTA) account for much of the reward associated with smoking: a single exposure to nicotine increases dopamine release in the nucleus accumbens for over an hour. Thus, when compared to placebos, nicotine replacement medications can double quit rates. However relapse within two years is common. Bupropion was first introduced as a clinical antidepressant in the 1980s, and is considered atypical due to the fact that it does not interact with most receptor classes, instead inhibiting dopamine and norepinephrine uptake. It is this atypical property that gives bupropion the qualities that led it to becoming the first antidepressant to be approved as a smoking cessation aid. Anti-smoking treatment with bupropion begins while the individual is smoking, and shows a much lower rate of relapse than nicotine replacement based treatments. As a broad spectrum antagonist of nicotinic acylcholine files without this message by purchasing novaPDF printer ( receptors, it is thought that buopropion counteracts the effects of nicotine in the mesolymbic dopamine system, however the exact mechanisms behind such a property are not yet fully understood. Mansvelder, Fagen, Chang, Mitchum and McGehee (2007) set out to explore the cellular effects of bupropion upon nicotine in the VTA by way of in Sprague-Dawley rats between ten to fourteen days of age were rapidly decapitated, their skulls and olfactory bulbs removed. A cut was made to the midbrain across the forth ventricle before placing the brain in an ice cold bath of cerebrospinal fluid. Up to three horizontal brain slices were obtained from the brain before incubating them for at least one hour at approximately thirty three degrees centigrade. If relevant to the test condition, bupropion was added at this point as Mansvelder et al found that bupropion often took up to twenty minutes to have any effect, as opposed to the more instantaneous action of nicotine. Once incubated, the experimental elements of nicotine tartrate, bicuculline methidodide,7-Dinitroquinoxaline-2,3-dione (DNQX) or bupropion HCl were applied through bath profusions. Bicuculline and DNQX were present in the bath at least 15 minutes before the effect of nicotine was assessed. Neurons were observed by way of an upright microscope and infra red illumination. Action potentials of the VTA were used as the primary means of observing nicotinic and bupropionic effect. A baseline action potential frequency was obtained from a 1 minute period prior to the addition of nicotine, and a one minute period was examined after peak nicotine effect - if no peak occurred, the period examined was one minute after nicotine application. A new brain slice was used for each experimental condition to ensure that neurons were exposed to a single test condition. To be noted is the fact that the Mansvelder et al (2007) only examined nicotinic and bupropionic effects upon naïve brains, and that the files without this message by purchasing novaPDF printer ( effects of prolonged or repeated exposure to either chemical may produce results inconstant with the findings of the study. Following previous studies’ illustration that dopamine neurons that project to the nucleus accumbens are depolarized by nicotine concentrations experienced by smokers, Mansvelder et al (2007) examined the action potential frequencies resulting from nicotinic and bupropionic exposure by way of recording from VTA dopamine uptake neurons. The findings from this confirmed that such an excitatory nicotinic effect does indeed occur, and furthermore that acute application of clinically relevant bupropion concentrations weakly effect this increased firing rate. Pretreatment with bupropion induces small increase of action potential firing rate over baseline in controls, but the effect is too week to ameliorate excitatory nicotinic effects. Glutamatergic transmission was isolated by adding bicuculline to block GABAergic synaptic inputs, and it was observed that nicotine drastically increased the frequency of spontaneous glutamatergic transmission in over half of the dopaminergic neurons of the VTA. Pretreatment with bupropion decreased this nicotinic effect by over seventy percent. This indicates that excitatory glutamatergic transmission in the VTA has a regulatory effect on dopamine neuron excitability, and that pretreatment with bupropion can inhibit the nicotinic effect on this system. By inhibiting the nicotine- induced inward current in dopamine neurons, and by reducing the nicotine-induced enhancement of excitatory transmission to these neurons, bupropion removes the excitatory effects of nicotine on the mesolimbic dopamine reward system. Previous studies have indicated that dopamine neurons within the VTA are regulated by inhibitory GABAergic inputs. Mansvelder et al (2007) examined VTA dopamine neurons receiving GABAergic inputs from local interneurons and projection files without this message by purchasing novaPDF printer ( fibers from the nucleus accumbens, and the ventral palladium, by way of specialized electrode recording of action potentials. Application of nicotine increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) threefold, relative to the pre- nicotine baseline. Pretreatment with buopropion inhibited this nicotinic effect by eighty five percent. Also of note is that pretreatment with buproprion inhibits baseline frequency of sIPSCs. These findings demonstrate that bupropion inhibits the majority of nicotinic acetycholine receptors (nAChRs) expressed by GABA neurons that project into the VTA dopamine neurons, but only weakly inhibits actual dopamine transport to the VTA. This suggests that inhibiting nicotinic receptors by way of bupropion treatment could remove excitatory cholinergic drive from GABA neurons, decreasing inhibitory drive to VTA dopamine receptive neurons, and facilitating the cessation of a nicotine addiction. This effect is strengthened if bupropion is administered to an individual in the early stages of nicotine addiction - clinical concentrations of bupropion dramatically reduce the effects of nicotine on synaptic transmission in the VTA – and thus bupropion may be a powerful aid in curbing the development of addiction. This study found that a clinical concentration of bupropion exposure for over one hour removes the excitatory actions of nicotine on the dopamine reward system. Though, in comparison with other commonly used antidepressants, buproprion has weak effects on dopamine re-uptake, its actions on the mesolimbic reward system, specifically inhibition of nAChRs, allow it to inhibit the excitatory effects of nicotine in the VTA. It is important to note that bupropion does not completely inhibit the cellular effects of nicotine upon the VTA. Considering the close linkage between mood stabilization and nicotine addiction, bupropion may be considered an optimum to simultaneously treat files without this message by purchasing novaPDF printer ( REFERENCE: Mansvelder, HD. Fagen, ZM. Chang, B. Mitchum, R. and McGehee, DS.
(2007) Bupropion inhibits the cellular effects of nicotine in the ventral tegmental area. Biochemical Pharmacology 74: 1283-1291. files without this message by purchasing novaPDF printer (

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