Nicotinic receptor-evoked hippocampal norepinephrine release is highly sensitive to inhibition by isoflurane

Westphalen, Robert I.; Gomez, Renato Santiago; Hemmings, Hugh C.

doi:10.1093/bja/aen387

Cited by 14 publications

(8 citation statements)

References 39 publications

(32 reference statements)

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“…The classical α7 nAChR antagonist, MLA, also potently (IC 50 = 275 nM) inhibited nicotine-evoked [ 3 H]NE, but maximal inhibition was incomplete (I max = 72%). The current results are consistent with a recent in vitro study which found that MLA (10 μM) inhibits nicotine (100 μM)-evoked [ 3 H]NE from rat hippocampal synaptosomes [51], and with in vivo microdialysis studies showing that MLA (microdialysis probe concentrations of 0.4 – 32 nM) inhibits nicotine-evoked NE release from rat hippocampus [52]. α7* nAChRs are thought to mediate NE release from hippocampus through an indirect mechanism, i.e., α7*-mediated stimulation of glutamate release, which in turn promotes NE release [53].…”

Section: Discussionsupporting

confidence: 93%

The novel nicotinic receptor antagonist, N,N′-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), inhibits nicotine-evoked [3H]norepinephrine overflow from rat hippocampal slices

Smith¹,

Dhawan²,

Zhang³

et al. 2009

Biochemical Pharmacology

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Smoking is a significant health concern and strongly correlated with clinical depression. Depression is associated with decreased extracellular NE concentrations in brain. Smokers may be self-medicating and alleviating their depression through nicotine stimulated norepinephrine (NE) release. Several antidepressants inhibit NE transporter (NET) function, thereby augmenting extracellular NE concentrations. Antidepressants, such as bupropion, also inhibit nicotinic receptor (nAChR) function. The current study determined if a recently discovered novel nAChR antagonist, N,N′-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), inhibits nicotine-evoked NE release from superfused rat hippocampal slices. Previous studies determined that bPiDDB potently (IC50 = 2 nM) inhibits nicotine-evoked striatal [3H]dopamine (DA) release in vitro, nicotine-evoked DA release in nucleus accumbens in vivo, and nicotine self-administration in rats. In the current study, nicotine stimulated [3H]NE release from rat hippocampal slices (EC50 = 50 μM). bPiDDB inhibited (IC50 = 430 nM; Imax = 90%) [3H]NE release evoked by 30 μM nicotine. For comparison, the nonselective nAChR antagonist, mecamylamine, and the α7 antagonist, methyllycaconitine, also inhibited nicotine-evoked [3H]NE release (IC50 = 31 and 275 nM, respectively; Imax = 91% and 72%, respectively). Inhibition by bPiDDB and mecamylamine was not overcome by increasing nicotine concentrations; Schild regression slope was different from unity, consistent with allosteric inhibition. Thus, bPiDDB was 200-fold more potent inhibiting nAChRs mediating nicotine-evoked [3H]DA release from striatum than those mediating nicotine-evoked [3H]NE release from hippocampus.

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Section: Discussionsupporting

confidence: 93%

The novel nicotinic receptor antagonist, N,N′-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), inhibits nicotine-evoked [3H]norepinephrine overflow from rat hippocampal slices

Smith¹,

Dhawan²,

Zhang³

et al. 2009

Biochemical Pharmacology

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“…Thus, nicotine may affect inhibition by interacting with dopaminergic systems that regulate reward and motivational processes (Viggiano et al, 2002). Similarly, nicotine has also been shown to stimulate the release of norepinephrine (Sterley et al, 2014; Westphalen et al, 2009; Zhao et al, 2007), which among other functions, modulates attention by regulating activity of prefrontal cortical neurons (Newman et al, 2008; McGaughy et al, 2008). We have previously shown that negative occasion setting is dependent on the prefrontal cortex (MacLeod & Bucci, 2010) and thus nicotine may act to enhance negative occasion setting by altering attentional functions mediated by prefrontal norepinephrine levels.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory learning is modulated by nicotinic acetylcholine receptors

2015

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Prior research has established that stimulating nicotinic acetylcholine receptors can facilitate learning and memory. However, most studies have focused on learning to emit a particular behavior, while little is known about the effects of nicotine on learning to withhold a behavioral response. The present study consisted of a dose response analysis of the effects of nicotine on negative occasion setting, a form of learned inhibition. In this paradigm, rats received one type of training trial in which presentation of a tone by itself was followed immediately by food reward. During the other type of trials, the tone was preceded by presentation of a light and no food was delivered after the tone. Rats gradually learned to approach the cup in anticipation of receiving food reward during presentations of the tone alone, but withheld that behavior when the tone was preceded by the light. Nicotine (0.35mg/kg) facilitated negative occasion setting by reducing the number of sessions needed to learn the discrimination between trial types and by reducing the rate of responding on non-reinforced trials. Nicotine also increased the orienting response to the light, suggesting that nicotine may have affected the ability to withhold food cup behavior on non-reinforced trials by increasing attention to the light. In contrast to the effects of nicotine, rats treated with mecamylamine (0.125, 0.5, or 2 mg/kg) needed more training sessions to discriminate between reinforced and non-reinforced trials compared to saline-treated rats. The findings indicate that nicotinic acetylcholine receptors may be active during negative occasion setting and that nicotine can potentiate learned inhibition.

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“…The hippocampus is critically involved in learning and memory processes (Lisman and Grace, 2005), and has been proposed as an important locus for anesthetic action (Pearce et al, 1989; Westphalen et al, 2009). Modulation of specific glutamatergic and dopaminergic signaling pathways supports anesthetic effects on transmitter release in mouse striatum in vivo (Snyder et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…It is likely that regional differences in anesthetic sensitivity also exist for other transmitters based on their distinct presynaptic regulatory mechanisms (Snyder et al, 2007; Verhage et al, 1992). This is exemplified by the more potent inhibition by isoflurane of acetylcholine-evoked norepinephrine release from hippocampal nerve terminals mediated by presynaptic nicotinic acetylcholine receptors (Westphalen et al, 2009), and by the lesser anesthetic sensitivity of neuropeptide transmitter release from large dense core vesicles (Pashkov and Hemmings, 2002). …”

Section: Discussionmentioning

confidence: 99%

Regional differences in the effects of isoflurane on neurotransmitter release

Westphalen¹,

Kwak²,

Daniels³

et al. 2011

Neuropharmacology

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Stimulus evoked neurotransmitter release requires that Na+ channel-dependent nerve terminal depolarization be transduced into synaptic vesicle exocytosis. Inhaled anesthetics block presynaptic Na+ channels and selectively inhibit glutamate over GABA release from isolated nerve terminals, indicating mechanistic differences between excitatory and inhibitory transmitter release. We compared the effects of isoflurane on depolarization-evoked [3H]glutamate and [14C]GABA release from isolated nerve terminals prepared from four regions of rat CNS evoked by 4-aminopyridine (4AP), veratridine (VTD), or elevated K+. These mechanistically distinct secretegogues distinguished between Na+ channel- and/or Ca2+ channel-mediated presynaptic effects. Isoflurane completely inhibited total 4AP-evoked glutamate release (IC50=0.42 ± 0.03 mM) more potently than GABA release (IC50=0.56 ± 0.02 mM) from cerebral cortex (1.3-fold greater potency), hippocampus and striatum, but inhibited glutamate and GABA release from spinal cord terminals equipotently. Na+ channel-specific VTD-evoked glutamate release from cortex was also significantly more sensitive to inhibition by isoflurane than was GABA release. Na+ channel-independent K+-evoked release was insensitive to isoflurane at clinical concentrations in all four regions, consistent with a target upstream of Ca2+ entry. Isoflurane inhibited Na+ channel-mediated (tetrodotoxin-sensitive) 4AP-evoked glutamate release (IC50=0.30 ± 0.03 mM) more potently than GABA release (IC50=0.67 ± 0.04 mM) from cortex (2.2-fold greater potency). The magnitude of inhibition of Na+ channel-mediated 4AP-evoked release by a single clinical concentration of isoflurane (0.35 mM) varied by region and transmitter: Inhibition of glutamate release from spinal cord was greater than from the three brain regions and greater than GABA release for each CNS region. These findings indicate that isoflurane selectively inhibits glutamate release compared to GABA release via Na+ channel-mediated transduction in the four CNS regions tested, and that differences in presynaptic Na+ channel involvement determine differences in anesthetic pharmacology.

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Nicotinic receptor-evoked hippocampal norepinephrine release is highly sensitive to inhibition by isoflurane

Cited by 14 publications

References 39 publications

The novel nicotinic receptor antagonist, N,N′-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), inhibits nicotine-evoked [3H]norepinephrine overflow from rat hippocampal slices

The novel nicotinic receptor antagonist, N,N′-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB), inhibits nicotine-evoked [3H]norepinephrine overflow from rat hippocampal slices

Inhibitory learning is modulated by nicotinic acetylcholine receptors

Regional differences in the effects of isoflurane on neurotransmitter release

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