Acute and chronic nicotine exposure differentially facilitate the induction of LTP

Fujii, Satoshi; Ji, Zhanxin; Morita, Nagayoshi; Sumikawa, Katumi

doi:10.1016/s0006-8993(99)01982-4

Cited by 190 publications

(158 citation statements)

References 18 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…These data provide a plausible parallel to reports that, 24 h after withdrawal from nicotine, mice given acute nicotine perform better in a hippocampal-dependent task (Davis et al, 2005) and that chronic nicotine improves spatial working memory in the radial arm maze (Levin et al, 1990(Levin et al, , 1996. In the CA1 and CA3 subfield of the hippocampus, chronic nicotine may act via more complex circuit changes (Fujii et al, 1999;Fujii and Sumikawa, 2001;Yamazaki et al, 2006a;Nakauchi et al, 2007).…”

Section: Possible Mechanisms In Substantia Nigrasupporting

confidence: 81%

Chronic Nicotine Cell Specifically Upregulates Functional α4* Nicotinic Receptors: Basis for Both Tolerance in Midbrain and Enhanced Long-Term Potentiation in Perforant Path

Nashmi

Xia²,

Deshpande³

et al. 2007

J. Neurosci.

248

320

View full text Add to dashboard Cite

Understanding effects of chronic nicotine requires identifying the neurons and synapses whose responses to nicotine itself, and to endogenous acetylcholine, are altered by continued exposure to the drug. To address this problem, we developed mice whose ␣4 nicotinic receptor subunits are replaced by normally functioning fluorescently tagged subunits, providing quantitative studies of receptor regulation at micrometer resolution. Chronic nicotine increased ␣4 fluorescence in several regions; among these, midbrain and hippocampus were assessed functionally. Although the midbrain dopaminergic system dominates reward pathways, chronic nicotine does not change ␣4* receptor levels in dopaminergic neurons of ventral tegmental area (VTA) or substantia nigra pars compacta. Instead, upregulated, functional ␣4* receptors localize to the GABAergic neurons of the VTA and substantia nigra pars reticulata. In consequence, GABAergic neurons from chronically nicotine-treated mice have a higher basal firing rate and respond more strongly to nicotine; because of the resulting increased inhibition, dopaminergic neurons have lower basal firing and decreased response to nicotine. In hippocampus, chronic exposure to nicotine also increases ␣4* fluorescence on glutamatergic axons of the medial perforant path. In hippocampal slices from chronically treated animals, acute exposure to nicotine during tetanic stimuli enhances induction of long-term potentiation in the medial perforant path, showing that the upregulated ␣4* receptors in this pathway are also functional. The pattern of cell-specific upregulation of functional ␣4* receptors therefore provides a possible explanation for two effects of chronic nicotine: sensitization of synaptic transmission in forebrain and tolerance of dopaminergic neuron firing in midbrain.

show abstract

Section: Possible Mechanisms In Substantia Nigrasupporting

confidence: 81%

Chronic Nicotine Cell Specifically Upregulates Functional α4* Nicotinic Receptors: Basis for Both Tolerance in Midbrain and Enhanced Long-Term Potentiation in Perforant Path

Nashmi

Xia²,

Deshpande³

et al. 2007

J. Neurosci.

248

320

View full text Add to dashboard Cite

show abstract

“…For example, nicotine acts via presynaptic ␣7 nAChRs in the ventral tegmental area to promote LTP (29). In the hippocampus, nicotine enhances LTP induction (52), and focal ACh application enhances LTP primarily through activation of postsynaptic nAChRs (37). Our data show that ␣7 nAChRs in the spinal cord may play both pre-and postsynaptic roles in long-term synaptic plasticity.…”

Section: Discussionmentioning

confidence: 72%

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Genzen

McGehee

2003

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Spinal administration of nicotinic agonists can produce both hyperalgesic and analgesic effects in vivo. The cellular mechanisms underlying these behavioral phenomena are not understood. As a possible explanation for nicotinic hyperalgesia, we tested whether nicotinic acetylcholine receptors (nAChRs) could enhance excitatory transmission onto spinal cord dorsal horn neurons. Whole-cell patch-clamp recordings were performed in neonatal rat spinal cord slices. Activation of nAChRs enhanced glutamatergic synaptic transmission in 59% of dorsal horn neurons tested, and this effect was blocked by methyllycaconitine (10 nM), suggesting a key role for ␣7 nAChRs. Inhibition of acetylcholinesterase with methamidophos also enhanced transmission, demonstrating a similar effect of endogenous acetylcholine. nAChR activation also enhanced transmission by dorsal root entry zone stimulation, suggesting that ␣7 nAChRs on the central terminals of DRG afferents mediate this effect. Paired pre-and postsynaptic stimulation induced long-term potentiation of excitatory inputs to some of the dorsal horn neurons. Long-term potentiation induction was much more prevalent when nicotine was applied during stimulation. This effect also depended on both ␣7 nAChRs and N-methyl-D-aspartate glutamate receptors. Our findings demonstrate that ␣7 nAChRs can contribute to both short-and long-term enhancement of glutamatergic synaptic transmission in the spinal cord dorsal horn and provide a possible mechanism for nicotinic hyperalgesia.E ffective pain management is a major challenge for modern healthcare. Most pain medications fall under two classes of compounds, opioids and nonsteroidal antiinflammatory drugs. Recently, structural analogs of nicotine have also demonstrated strong analgesic potency (1, 2). Although these agents may provide alternate pain therapies, a number of issues remain to be resolved, such as addictive profiles and side effects, including paradoxical hyperalgesia. Considerable research has focused on the analgesic effects of nicotine and its analogs (2-7), yet the mechanisms underlying nicotinic hyperalgesia are not well understood.Hyperalgesia and͞or irritation have been observed after central injections of nicotinic agonists (8-10), systemic injections of subanalgesic doses (11), and intrathecal applications (12,13). This intrathecal effect is associated with significant increases in excitatory transmitter release (14), and both nicotinic and glutamate receptor antagonists can decrease this hyperalgesia (15, 16). Although dorsal horn neurons are excited by nicotine (17), it is not known which subtypes of nicotinic acetylcholine receptors (nAChRs) are expressed by dorsal horn neurons or on presynaptic afferent terminals. For example, nicotinic enhancement of synaptic activity has been noted in the spinal cord dorsal horn (SCDH) in mice that lack the ␣4 nAChR subunit, but the nAChR subtype(s) that mediate this effect is unknown (5).Neuronal nAChRs are pentameric ligand-gated ion channels, and molecular cloning has identified nin...

show abstract

“…Thus, it is proposed that nAChRs may play crucial roles in LTP. Indeed, nicotine facilitates LTP induction in hippocampal slice preparations (6). Moreover, we showed that intraperitoneal application of nicotine caused a long-lasting potentiation, which was named nicotinic LTP (LTPn), in vivo in the intact mouse dentate gyrus (7), suggesting that the intact preparation is especially relevant because all of the normal neural connections of the hippocampal formation are preserved.…”

Section: Introductionmentioning

confidence: 98%

Epibatidine Induces Long-Term Potentiation (LTP) via Activation of α4β2 Nicotinic Acetylcholine Receptors (nAChRs) In Vivo in the Intact Mouse Dentate Gyrus: Both α7 and α4β2 nAChRs Essential to Nicotinic LTP

Matsuyama

Matsumoto

2003

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. Activation of nicotinic acetylcholine receptors (nAChRs) induces nocotinic longterm potentiation (LTPn) in vivo in the mouse dentate gyrus. We have found that a4b2 nAChRs activated by epibatidine induce LTPn, the full size of which requires the involvement of a4b 2 and a 7 nAChRs, in the intact mouse dentate gyrus using extracellular recording techniques. Intraperitoneal application of epibatidine, a potent a 4b2 nAChR agonist, at 0.3 -3.0 mg / kg induced a long-lasting increase similar to LTPn induced by choline, a selective a 7 nAChR agonist, and at 10 mg / kg caused a transient increase followed by a depression. The LTPn induced by epibatidine at 3.0 m g / kg or choline at 30 mg/ kg was significantly suppressed by pre-treatment but not post-treatment with mecamylamine (0.5 mg / kg, i.p.), a non-selective neuronal nicotinic antagonist. Post-application of nicotine at 3.0 mg / kg enhanced epibatidine-induced LTPn to the same level of nicotine-induced LTPn, but post-application of epibatidine had no effect on nicotine-induced LTPn. Epibatidine-induced LTPn was additionally increased by post-application of choline, and vice versa, reaching the same level of nicotine-induced LTPn. The present study revealed that epibatidine induced the LTPn via a 4b2 nAChRs and that both a 7 and a4b 2 nAChRs were essential for full-sized LTPn, suggesting that both nAChRs play an important role in synaptic plasticity.

show abstract

Acute and chronic nicotine exposure differentially facilitate the induction of LTP

Cited by 190 publications

References 18 publications

Chronic Nicotine Cell Specifically Upregulates Functional α4* Nicotinic Receptors: Basis for Both Tolerance in Midbrain and Enhanced Long-Term Potentiation in Perforant Path

Chronic Nicotine Cell Specifically Upregulates Functional α4* Nicotinic Receptors: Basis for Both Tolerance in Midbrain and Enhanced Long-Term Potentiation in Perforant Path

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Epibatidine Induces Long-Term Potentiation (LTP) via Activation of α4β2 Nicotinic Acetylcholine Receptors (nAChRs) In Vivo in the Intact Mouse Dentate Gyrus: Both α7 and α4β2 nAChRs Essential to Nicotinic LTP

Contact Info

Product

Resources

About