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

doi:10.1016/j.neuropharm.2004.09.005

Neuropharmacology

Volume 48, Issue 1, January 2005, Pages 72-79

https://doi.org/10.1016/j.neuropharm.2004.09.005 Get rights and content

Abstract

Different nicotinic acetylcholine receptor subtypes appear to modulate dopamine release from the striatum and prefrontal cortex. In this study a combination of subtype-selective antagonists and agonists were used to extensively characterize the nAChRs involved in dopamine release from slice preparations of these two brain regions. α-conotoxin-MII inhibited nicotine-evoked [³H]dopamine (DA) release from striatum by 45%, but did not affect cortical dopamine release. Neither methyllycaconitine, α-bungarotoxin, nor α-conotoxin-ImI affected nicotine-evoked [³H]DA release from either striatum or prefrontal cortex. MG 624, a novel selective nAChR antagonist, inhibited cortical [³H]DA by 53%, but had no effect on striatal release. Compared to nicotine, (±)-UB-165 showed less efficacy with respect to dopamine release from striatum, and had no effect on cortical dopamine release. (±)-UB-165-evoked striatal dopamine release was completely blocked by mecamylamine, partially blocked (up to 55%) by α-conotoxin-MII, and unaffected by methyllycaconitine or α-conotoxin-ImI. α4β2* and α6β2β3* nAChRs appear to play a role in striatal dopamine release, whereas α4β2* nAChRs modulate release from prefrontal cortex. α7* nAChRs do not appear to play a role in nAChR-mediated dopamine release from either brain region.

Introduction

Functional nicotinic acetylcholine receptors (nAChRs), existing as heteromeric complexes comprised of α (α2–α6) and β (β2–β4) subunits, or homomeric complexes comprised of five α (α7–α8) subunits, have been identified throughout the central nervous system (for review, see Romanelli and Gualtieri, 2003). Additionally, two other nAChR subunits, α9 and α10, have been identified in the hair cells of the inner ear (Elgoyhen et al., 1994, Elgoyhen et al., 2001), and the dorsal root ganglia (Lips et al., 2002). A major role of nAChRs is in the modulation of neurotransmitter release (Role and Berg, 1996). Neurotransmitter release can be significantly affected by activation of nAChRs. For example, nAChR activation can cause a robust stimulation in dopamine (DA) release from several areas of the brain (Puttfarcken et al., 2000, Grady et al., 2002). The ability of nAChRs to modulate DA release is of particular interest because of the roles that DA can play in various brain functions, including cognition, locomotion, and reward. Since various nAChR subunit combinations can form functional receptors with varied physiological and pharmacological profiles, the potential exists for extensive diversity in the function of these receptors to regulate neurotransmitter release. Indeed, previous studies from our laboratory have shown that nicotine-evoked [³H]dopamine ([³H]DA) release from slices of rat striatum and prefrontal cortex is mediated by distinct nAChRs (Puttfarcken et al., 2000). In these studies, the role of α3- vs. α4-containing nAChRs in [³H]DA release from striatum and cortex was investigated. The goal of the present study was to further investigate the involvement of specific nAChRs in [³H]DA release from these two regions. The ability of the α7-selective antagonists, methyllycaconitine (MLA) (Alkondon et al., 1992), α-bungarotoxin (α-BTX) (Chen and Patrick, 1997), α-conotoxin ImI (α-CtxImI) (McIntosh et al., 1994), and the α3β2β3* (* indicates possibility of other unidentified subunits present) and/or α6β2β3* antagonist, α-conotoxin MII (α-CtxMII) (Cartier et al., 1996, Champtiaux et al., 2002), to affect [³H]DA release from both regions was examined. N,N,N-Triethyl-2-[4-(2-phenylethenyl) phenoxy] ethanaminium iodine (MG 624), a compound reported to be selective toward the α7-containing receptors in chick (Gotti et al., 1998, Gotti et al., 2000), was also examined. Finally, in combination with these studies, the release evoked by two agonists with distinct receptor subtype selectivity, (−)-nicotine and (±)-UB-165, was characterized. To our knowledge, this is the first study to characterize the pharmacological actions of MG 624 on nicotine-evoked [³H]DA release from either region, where very little is known regarding its selectivity toward non-α7-containing nAChRs in rodent brain. In addition, it is also the first study to examine the effects of the nicotinic agonist, (±)-UB-165, in the prefrontal cortex.

Section snippets

Materials

[³H]Dopamine ([³H]DA) (3,4-[ring-2,5,6-³H]dihydroxyphenylethylamine, 60 Ci/mmol) was purchased from Perkin Elmer Life Science (Boston, MA). (−)-Nicotine bitartrate, mecamylamine (Mec), MLA, desipramine, pargyline and ascorbic acid were purchased from Sigma (St. Louis, MO). Nomifensine was purchased from Sigma-RBI (Natick, MA). α-CtxMII was obtained from Tocris (Bristol, UK). (±)-UB-165 fumarate, and MG 624 were obtained from Tocris (Ellisville, MO). α-CtxImI was purchased from either American

The effect of α-CtxMII on nicotine-evoked [³H]DA release from striatum and prefrontal cortex

Multiple experiments performed within each study indicate that the maximal amount of release evoked by nicotine is different between striatum and prefrontal cortex (striatum=2.7±0.1%, $n = 26;$ prefrontal cortex=2.0±0.1%, $n = 30$ ), suggesting regional differences in distribution, expression and/or type of nAChR subtype(s) involved, as well as the extent of dopaminergic innervation.

Subsequent studies compared the ability of 120 nM α-CtxMII, a concentration previously found to inhibit anatoxin-a- (

Discussion

Previous reports from our laboratory (Puttfarcken et al., 2000), as well as others, have described studies on the characterization of nAChR-mediated [³H]DA release from striatum (Sacaan et al., 1995, Sharples et al., 2000, Whiteaker et al., 1995) and, to some extent, from cortex (Whiteaker et al., 1995). The present study has extended these studies by investigating the involvement of other nAChRs in striatum and prefrontal cortex.

Initial studies examined the ability of α-CtxMII to affect

Acknowledgements

The authors wish to thank Dr. Clark Briggs, Dr. Wilfried Hornberger, Dr. Michael Meyer, and Dr. Susan Wonnacott for their helpful comments on the manuscript.

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

Abstract

Introduction

Section snippets

Materials

The effect of α-CtxMII on nicotine-evoked [3H]DA release from striatum and prefrontal cortex

Discussion

Acknowledgements

Neuropharmacology

Journal of Biological Chemistry

Journal of Biological Chemistry

Cell

Behavioural Brain Research

Neuropharmacology

Neuroscience

Journal of Biological Chemistry

European Journal of Pharmacology

Neuropharmacology

Neuron

Blockade of nicotinic currents in hippocampal neurons defines methyllycaconitine as a potent and specific receptor antagonist

Molecular Pharmacology

Expression of neuronal nicotinic acetylcholine receptor subunit mRNAs within midbrain dopamine neurons

Journal of Comparative Neurology

Distribution and pharmacology of α6-containing nicotinic acetylcholine receptors analyzed with mutant mice

Journal of Neuroscience

Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice

Journal of Neuroscience

Release of [3H]noradrenaline from rat hippocampal synaptosomes by nicotine: mediation by different nicotinic receptor subtypes from striatal [3H]dopamine release

British Journal of Pharmacology

α10: a determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells

Proceedings of the National Academy of Science USA

Stable expression, pharmacological properties and regulation of the human neuronal nicotinic acetylcholine α4β2 receptor

Journal of Pharmacology and Experimental Therapeutics

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

The effect of α-CtxMII on nicotine-evoked [³H]DA release from striatum and prefrontal cortex

Release of [³H]noradrenaline from rat hippocampal synaptosomes by nicotine: mediation by different nicotinic receptor subtypes from striatal [³H]dopamine release