Dual effects of nicotine on dopamine neurons mediated by different nicotinic receptor subtypes

Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
The International Journal of Neuropsychopharmacology (Impact Factor: 5.26). 04/2003; 6(1):1-11. DOI: 10.1017/S1461145702003188
Source: PubMed

ABSTRACT Burst firing of dopaminergic neurons has been found to represent a particularly effective means of increasing dopamine release in terminal areas as well as activating immediate early genes in dopaminoceptive cells. Spontaneous burst firing is largely controlled by the level of activation of NMDA receptors in the ventral tegmental area (VTA) as a consequence of glutamate released from afferents arising mainly in the prefrontal cortex. Nicotine has been found to effectively increase burst firing of dopaminergic cells. This effect of nicotine may be due to an alpha 7 nicotinic receptor-mediated presynaptic facilitation of glutamate release in the VTA. By the use of in-vivo single-cell recordings and immunohistochemistry we here evaluated the role of alpha 7 nicotinic receptors in nicotine-induced burst firing of dopamine cells in the VTA and the subsequent activation of immediate early genes in dopaminoceptive target areas. Nicotine (0.5 mg/kg s.c.) was found to increase firing rate and burst firing of dopaminergic neurons. In the presence of methyllycaconitine (MLA, 6.0 mg/kg i.p.) nicotine only increased firing rate. Moreover, in the presence of dihydro-beta-erythroidine (DH beta E, 1.0 mg/kg i.p.), an antagonist at non-alpha 7 nicotinic receptors, nicotine produced an increase in burst firing without increasing the firing rate. Nicotine also increased Fos-like immunoreactivity in dopamine target areas, an effect that was antagonized with MLA but not with DH beta E. Our data suggest that nicotine's augmenting effect on burst firing is, indeed, due to stimulation of alpha 7 nicotinic receptors whereas other nicotinic receptors seem to induce an increase in firing frequency.

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Available from: Monica Mameli Engvall, Jan 30, 2015
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    • "Such features equip ␣7 nAChR for a role in synaptic plasticity (Mansvelder and McGehee, 2000; McKay et al., 2007). Glutamate release, and its enhancement via ␣7 nAChRs, has been implicated in the switch to burst firing in the VTA, mediated by NMDA receptors (Chergui et al., 1993; Overton and Clark, 1997; Schilström et al., 2003). "
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    • "This increase in basal or background DA measured by microdialysis in the NAc shell is considered indicative of a drug's addictive influence. Nicotine, at the concentration obtained from tobacco, induces phasic bursts from VTA/SNc DA neurons (Figure 1b) that innervate much of the dorsal to ventral extent of the striatum (Grenhoff et al. 1986, Pidoplichko et al. 1997, Schilstrom et al. 2003, Zhang et al. 2009b), suggesting that the DA signal should be comparable throughout the striatum. However , nicotinic and other local striatal mechanisms regulate the frequency dependence of DA release (Cragg 2003, Rice & Cragg 2004, Zhang et al. 2009a, Zhang & Sulzer 2004, Zhou et al. 2001). "
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    • "Dopamine system activation is thought to account for the rewarding properties of nicotine and may also partially account for nicotine-associated improvements in attention and memory [3]. Nevertheless, the functional roles played by distinct subtypes of nicotinic receptors relative to the dopamine system remain to be fully elucidated. "
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