Different nicotinic acetylcholine receptor subtypes mediating striatal and prefrontal cortical [3H]dopamine release

Cao, Ying-Jun; Surowy, Carol S.; Puttfarcken, Pamela S.

doi:10.1016/j.neuropharm.2004.09.005

Cited by 66 publications

(53 citation statements)

References 32 publications

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“…2A). These results are generally consistent with previous reports of nicotine-evoked DA release in rodent prefrontal cortex slices (Rao et al, 2003;Cao et al, 2005). Perfusion with soluble 100nM of Aβ (Fig.…”

Section: Nicotine and β-Amyloid Evoke The Release Of Dopamine In Moussupporting

confidence: 92%

Dopamine release in prefrontal cortex in response to β-amyloid activation of α7∗ nicotinic receptors

Khan

Nichols

2007

Brain Research

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The levels of soluble beta amyloid (Aβ) are correlated with symptom severity in Alzheimer's disease. Soluble Aβ has been shown to disrupt synaptic function and it has been proposed that accumulation of soluble Aβ triggers synapse loss over the course of the disease. Numerous studies indicate that soluble Aβ has multiple targets, one of which appears to be the nicotinic acetylcholine receptor, particularly for Aβ concentrations of pM-nM. Moreover, pM-nM soluble Aβ was found to increase presynaptic Ca 2+ levels, suggesting that it may have an impact on neurotransmitter release. In the present study, soluble Aβ was perfused into mouse prefrontal cortex and the effect on the release of dopamine outflow via microdialysis was assessed. In the presence of tetrodotoxin, Aβ 1-42 at 100nM evoked the release of dopamine to ∼170% of basal levels. The Aβ 1-42 -evoked dopamine release was sensitive to antagonists of α7 nicotinic receptors and was absent in mice harboring a null mutation for the α7 nicotinic subunit, but was intact in mice harboring a null mutation for the β2 nicotinic subunit. The control peptide Aβ 40-1 was without effect. In contrast, Aβ 1-42 at 1-10pM caused a profound but slowly developing decrease in dopamine outflow. These results suggest that Aβ alters dopamine release in mouse prefrontal cortex, perhaps involving distinct targets as it accumulates during Alzheimer's disease and leading to disruption of synaptic signaling.

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Section: Nicotine and β-Amyloid Evoke The Release Of Dopamine In Moussupporting

confidence: 92%

Dopamine release in prefrontal cortex in response to β-amyloid activation of α7∗ nicotinic receptors

Khan

Nichols

2007

Brain Research

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“…Increased presynaptic [Ca 2+ ]i likely underlies the nicotine-evoked release of neurotransmitter from cortical synaptosomes described previously to involve predominantly α7 nAChRs whose activation, in turn, triggers the opening of N-and P/Q-type VGCCs [25,26], though β2 nAChRs are likely involved as well [27,28]. In addition, increased presynaptic [Ca 2+ ]i also likely underlies nicotine enhancement of neurotransmitter release measured in cortical slices [29][30][31][32][33] and the intact cortex using microdialysis [19,34,35].…”

Section: Presynaptic Ca 2+ Responses Following Chronic Treatment Withmentioning

confidence: 82%

Chronic Nicotine Alters Nicotinic Receptor-induced Presynaptic Ca2+ Responses in Isolated Nerve Terminals

Dougherty

Mehta

et al. 2007

Neurochem Res

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Brain nicotinic receptors display pronounced permeability for Ca 2+ and localize to presynaptic nerve terminals, in addition to postsynaptic sites. Chronic exposure to nicotine has been shown to alter brain nicotinic receptor expression, but the functional consequences for presynaptic Ca 2+ have not been directly examined. Here, we used confocal imaging to assess Ca 2+ responses in individual nerve terminals from cortices of mice treated up to 14 days with nicotine as compared to vehicle-treated controls. Chronic nicotine treatment led to substantially enhanced amplitudes of presynaptic Ca 2+ responses to acute application of nicotine at concentrations of 50 nM (2-fold) and 500 nM (1.7-fold), but not 50 μM. In addition, increased expression of high-affinity nicotinic receptors on isolated terminals was observed following chronic treatment, as determined immunocytochemically and pharmacologically. These findings suggest that chronic exposure to nicotine may lead to enhanced sensitivity to nicotine at select presynaptic sites in brain via upregulation of high-affinity nicotinic receptors.

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“…3 H]DA release from rat striatal slices (Cao et al, 2005), indicating that ␣7* nAChRs do not play a major role in mediating this response.…”

Section: Discussionmentioning

confidence: 94%

N,N′-Alkane-diyl-bis-3-picoliniums as Nicotinic Receptor Antagonists: Inhibition of Nicotine-Evoked Dopamine Release and Hyperactivity

Dwoskin

Wooters

Sumithran

et al. 2008

J Pharmacol Exp Ther

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The current study evaluated a new series of N, analogs with C 6 -C 12 methylene linkers as nicotinic acetylcholine receptor (nAChR) antagonists, for nicotine-evoked [ 3 H]dopamine (DA) overflow, for blood-brain barrier choline transporter affinity, and for attenuation of discriminative stimulus and locomotor stimulant effects of nicotine. bAPi analogs exhibited little affinity for ␣4␤2* (* indicates putative nAChR subtype assignment) and ␣7* high-affinity ligand binding sites and exhibited no inhibition of DA transporter function. With the exception of C 6 , all analogs inhibited nicotine-evoked [ 3 H]DA overflow (IC 50 ϭ 2 nM-6 M; I max ϭ 54 -64%), with N, C 12 ) being most potent. bPiDDB did not inhibit electrically evoked [ 3 H]DA overflow, suggesting specific nAChR inhibitory effects and a lack of toxicity to DA neurons. Schild analysis suggested that bPiDDB interacts in an orthosteric manner at nAChRs mediating nicotine-evoked [ 3 H]DA overflow.To determine whether bPiDDB interacts with ␣-conotoxin MIIsensitive ␣6␤2-containing nAChRs, slices were exposed concomitantly to maximally effective concentrations of bPiDDB (10 nM) and ␣-conotoxin MII (1 nM). Inhibition of nicotine-evoked [ 3 H]DA overflow was not different with the combination compared with either antagonist alone, suggesting that bPiDDB interacts with ␣6␤2-containing nAChRs. C 7 , C 8 , C 10 , and C 12 analogs exhibited high affinity for the blood-brain barrier choline transporter in vivo, suggesting brain bioavailability. Although none of the analogs altered the discriminative stimulus effect of nicotine, C 8 , C 9 , C 10 , and C 12 analogs decreased nicotine-induced hyperactivity in nicotine-sensitized rats, without reducing spontaneous activity. Further development of nAChR antagonists that inhibit nicotine-evoked DA release and penetrate brain to antagonize DA-mediated locomotor stimulant effects of nicotine as novel treatments for nicotine addiction is warranted.Nicotine, the principal tobacco alkaloid, is an agonist at neuronal nicotinic acetylcholine receptor (nAChR) subtypes modulating dopamine (DA) release. Habitual tobacco smoking is maintained via rapid nicotine delivery to brain (Le Foll and Goldberg, 2006) and results from the intrinsic rewarding properties of nicotine, believed to be due to increased DA release. Classical nAChR antagonists mecamylamine and dihydro-␤-erythroidine (DH␤E) inhibit nicotine-evoked DA release and decrease the locomotor stimulant and reinforcing effects of nicotine in rats Watkins et al., 1999;Rahman et al., 2004), suggesting a role for nAChRmediated DA release in these abuse-related behavioral efThis research was supported by National Institutes of Health Grants K02 DA00399, T32 DA007304, and U19 DA017548.Potential royalty payments to L.P.D., P.A.C., and J.T.A. may occur consistent with the University of Kentucky policy.Article, publication date, and citation information can be found at

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Different nicotinic acetylcholine receptor subtypes mediating striatal and prefrontal cortical [3H]dopamine release

Cited by 66 publications

References 32 publications

Dopamine release in prefrontal cortex in response to β-amyloid activation of α7∗ nicotinic receptors

Dopamine release in prefrontal cortex in response to β-amyloid activation of α7∗ nicotinic receptors

Chronic Nicotine Alters Nicotinic Receptor-induced Presynaptic Ca2+ Responses in Isolated Nerve Terminals

N,N′-Alkane-diyl-bis-3-picoliniums as Nicotinic Receptor Antagonists: Inhibition of Nicotine-Evoked Dopamine Release and Hyperactivity

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