The Neurobiological Bases for the Pharmacotherapy of Nicotine Addiction

Abstract

Nicotine, the major psychoactive agent present in tobacco, acts as a potent addictive drug both in humans and laboratory animals, whose locomotor activity is also stimulated. A large body of evidence indicates that the locomotor activation and the reinforcing effects of nicotine may be related to its stimulatory effects on the mesolimbic dopaminergic function. Thus, it is now well established that nicotine can increase in vivo DA outflow in the nucleus accumbens and the corpus striatum. The stimulatory effect of nicotine on DA release most probably results from its ability to excite the neuronal firing rate and to increase the bursting activity of DA neurons in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), and from its stimulatory action on DA terminals in the corpus striatum and the nucleus accumbens. The neurochemical data are consistent with neuroanatomical findings showing the presence of nicotinic acetylcholine receptors (nAChRs) in the SNc, the VTA, and in projection areas of the central dopaminergic system such as the corpus striatum and the nucleus accumbens. Several lines of evidence indicate that the reinforcing properties of drugs of abuse, including nicotine, can be affected by a number of transmitter systems which may act by modulating central dopaminergic function. In this paper, the neurobiological mechanisms underlying nicotine addiction will be reviewed, and the possible strategies for new pharmacological treatments of nicotine dependence will be examined.

Nitric Oxide Modulation of the Basal Ganglia Circuitry: Therapeutic Implication for Parkinson's Disease and Other Motor Disorders

“…Similar results have been obtained in vivo: disruption of NO levels by general treatment or local application by microiontophoresis with L-NAME, L-ARG and the NO donor molsidomine (MOL) produced consistent changes in the firing rate and burst firing of SNc DA neurons [44]. Consistent with a block of NMDA-induced bursts in vitro by NOS inhibition [51], disrupting NO endogenous tone counteracted the stimulation induced by nicotine in the SNc [44] and in VTA [52] (see [53] for the nicotine effect in the DA function). 7-nitro-indazolone (7-NI) and L-NAME pretreatment completely prevented the increase in DA neuronal firing rate and burst firing induced by nicotine administration in the SNc and attenuated nicotine-induced enhancement of the extracellular levels of DA and 3,4-dihydroxy-phenylacetic acid (DOPAC) in the striatum of awake freely moving rats [44].…”

Smoking, nicotine and neuropsychiatric disorders

“…CRF, endogenous opioids, and orexins). For details on the relevance of these diverse actions of NIC in various brain functions and in the development and maintenance of NIC dependence, (see De Biasi and Salas, 2008;Di Matteo et al, 2007;Touiki et al, 2007Touiki et al, , 2008Seth et al, 2002;Galindo-Charles et al, 2008;Rossi et al, 2005a,b;Grilli et al, 2005;Markou, 2007Markou, , 2008Liechti and Markou, 2008;Kenny et al, 2009;Hahn and Stolerman, 2005;Erhardt et al, 2000;George et al, 2007;Xue and Domino, 2008;Chen et al, 2008b;Merritt et al, 2008;Pasumarthi and Fadel, 2008).…”

Nicotine derived from the electronic cigarette improves time-based prospective memory in abstinent smokers

“…Nicotine is a cholinergic agonist, binding to presynaptic nicotinic acetylcholine receptors (nAChRs) in turn facilitating the release of a number of neurotransmitters including acetylcholine, dopamine, serotonin and glutamate (Di Matteo et al 2007). The cholinergic neurotransmitter system is generally considered to play a pivotal role in memory and attention modulation (Kruk-Slomka et al 2012;Robins and Roberts 2007).…”