Inhibition of nicotine-induced hippocampal norepinephrine release in rats by alpha-conotoxins MII and AuIB microinjected into the locus coeruleus

doi:10.1016/S0304-3940(99)00293-1

Neuroscience Letters

Volume 266, Issue 2, 7 May 1999, Pages 113-116

https://doi.org/10.1016/S0304-3940(99)00293-1 Get rights and content

Abstract

Hippocampal norepinephrine (NE) is secreted by neurons projecting from the locus coeruleus (LC) to the hippocampus; LC nicotinic receptors (NAchRs) are involved in the effects of systemic nicotine on this pathway. To clarify the NAchR subtypes, NAchR antagonists, termed α-conotoxins, were microinjected into the LC before nicotine; MII and AulB were used to assess the potential involvement of α3β2 and α3β4 subunit-containing NAchRs, respectively. Nicotine dose-dependently stimulated hippocampal NE release (P<0.01). MII (>0.25 pmol) reduced the NE response to nicotine (67% decrease; P<0.05), as did AuIB (44% reduction by 25 pmol; P<0.05). Administered together, however, MII and AuIB were no more effective than MII. Thus, MII and AuIB are capable of interacting with NAchR subtypes other than those previously defined as α3β2 and α3β4, respectively. NAchRs containing both β2 and β4subunits may be involved.

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Acknowledgements

This work is supported by NIDA DA03977 (to B.M.S.), MH53631 and GM48677 (to J.M.M.).

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Citation Excerpt :
These postsynaptic events were blocked by 100 μM but not 3 μM DHβE indicating that these receptors are heteromeric nicotinic receptors and non-α4β2 receptors. This study focused on the role of α3β2 and/or α6βX containing, and α3β4 nicotinic receptors, using the selective neurotoxins, α-conotoxin MII and α-conotoxin AuIB, respectively (Cartier et al., 1996; Luo et al., 1998; Fu et al., 1999; Grady et al., 2001). The results from this study demonstrate there are several populations of nicotinic receptors that differentially affect postsynaptic glutamatergic neurotransmission in cardiac vagal neurons.
Nicotinic receptors play an essential role in central cardiorespiratory function, however, the types of nicotinic receptors responsible for activating cardiac vagal neurons in the nucleus ambiguus that control heart rate are unknown. This study tests whether α-conotoxin MII and α-conotoxin AuIB sensitive nicotinic receptors are involved in augmentation of glutamatergic neurotransmission and changes in holding current in cardiac vagal neurons, and whether exposure to nicotine in the prenatal period alters these responses. The nicotinic agonist cytisine significantly increased the holding current and amplitude of glutamatergic mEPSCs. In unexposed animals α-conotoxin MII (100 nM) significantly reduced the increase in mEPSC amplitude and change in holding current evoked by cytisine. However, in animals prenatally exposed to nicotine, α-conotoxin MII blunted but did not block the increase in mEPSC amplitude but blocked the increase in holding current evoked by cytisine. In unexposed animals, α-conotoxin AuIB (10 μM) blocked the cytisine evoked increase in mEPSC amplitude and inhibited but did not abolish the increase in holding current. In contrast, in animals exposed to nicotine, α-conotoxin AuIB blunted the increase in mEPSC amplitude, and completely abolished the cytisine evoked increase in holding current. These data demonstrate that the prenatal nicotine exposure alters the nicotinic receptors involved in excitation of cardiac vagal neurons.

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Inhibition of nicotine-induced hippocampal norepinephrine release in rats by alpha-conotoxins MII and AuIB microinjected into the locus coeruleus

Abstract

Section snippets

Acknowledgements

J. Biol. Chem.

Adv. Pharmacol.

J. Biol. Chem.

Noradrenergic mechanisms in stress and anxiety. I. preclinical studies

Synapse

β-subunit co-determine the sensitivity of rat neuronal nicotinic receptors to antagonists

Pfluguers Arch.-Eur. J. Physiol.

Nicotinic receptor subtypes in the developing chick brain: appearance of a species containing the α4, β2, and α5 gene products

Mol. Pharmacol.

Nicotine-induced norepinephrine release in the rat amygdala and hippocampus is mediated through brainstem nicotinc cholinergic receptors

J. Pharmacol. Exp. Ther.

Adrenocorticotropin response and nicotine-induced norepinephrine secretion in the rat paraventricular nucleus are mediated through brainstem receptors

Endocrinology

The neuronal alpha6subunit forms functional heteromeric acetylcholine receptors in human transfected cells

Eur. J. Neurosci.

Immunohistochemical localization of the nicotinic acetylcholine receptor subunit alpha6 to dopaminergic neurons in the substantial nigra and ventral tegmental area

NeuroReport