Presynaptic nicotinic receptors modulating dopamine release in the rat striatum

Wonnacott, Susan; Kaiser, Sergio; Mogg, Adrian J.; Soliakov, L.; Jones, Ian W.

doi:10.1016/s0014-2999(00)00005-4

Cited by 209 publications

(178 citation statements)

References 28 publications

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“…It is also possible that a component of either or both the behavioral and dopamine effects could be indirect via activity at acetylcholine receptors on NAc glutamate terminals. Indeed, cholinergic modulation of striatal dopamine release has been demonstrated, under some conditions, to be sensitive to glutamate receptor antagonists (Cachope et al, 2012;Wonnacott et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

Collins¹,

Aitken²,

Greenfield³

et al. 2016

Neuropsychopharmacol

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Environmental reward-predictive cues can motivate reward-seeking behaviors. Although this influence is normally adaptive, it can become maladaptive in disordered states, such as addiction. Dopamine release in the nucleus accumbens core (NAc) is known to mediate the motivational impact of reward-predictive cues, but little is known about how other neuromodulatory systems contribute to cue-motivated behavior. Here, we examined the role of the NAc cholinergic receptor system in cue-motivated behavior using a Pavlovian-to-instrumental transfer task designed to assess the motivating influence of a reward-predictive cue over an independently-trained instrumental action. Disruption of NAc muscarinic acetylcholine receptor activity attenuated, whereas blockade of nicotinic receptors augmented cue-induced invigoration of reward seeking. We next examined a potential dopaminergic mechanism for this behavioral effect by combining fast-scan cyclic voltammetry with local pharmacological acetylcholine receptor manipulation. The data show evidence of opposing modulation of cue-evoked dopamine release, with muscarinic and nicotinic receptor antagonists causing suppression and augmentation, respectively, consistent with the behavioral effects of these manipulations. In addition to demonstrating cholinergic modulation of naturally-evoked and behaviorally-relevant dopamine signaling, these data suggest that NAc cholinergic receptors may gate the expression of cue-motivated behavior through modulation of phasic dopamine release.

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Section: Discussionmentioning

confidence: 99%

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

Collins¹,

Aitken²,

Greenfield³

et al. 2016

Neuropsychopharmacol

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“…In this study, we identified reduced Chrnα6 expression in ak striata. α6-subunit containing nicotinic receptors are selectively expressed on dopaminergic terminals in the striatum (Wonnacott et al, 2000;Zoli et al, 2002). Therefore, it is possible that reduced Chrnα6 expression reflects a presynaptic striatal alteration due to the failure of dorsal striatonigral afferents to develop in these mice (Nunes et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Motor deficits and altered striatal gene expression in aphakia (ak) mice

et al. 2007

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Like humans with Parkinsons disease (PD), the ak mouse lacks the majority of the substantia nigra pars compacta (SNc) and experiences striatal denervation. The purpose of this study was to test whether motor abnormalities in the ak mouse progress over time, and whether motor function could be associated with temporal alterations in the striatal transcriptome. Ak and wt mice (28 to 180 days old) were tested using paradigms sensitive to nigrostriatal dysfunction. Results were analyzed using a linear mixed model. Ak mice significantly underperformed wt controls in rotarod, balance beam, string test, pole test and cotton shred tests at all ages examined. Motor performance in ak mice remained constant over the first 6 months of life, with the exception of the cotton shred test, in which ak mice exhibited marginal decline in performance. Dorsal striatal semi-quantitative RT-PCR for 19 dopaminergic, cholinergic, glutaminergic and catabolic genes was performed in 1 and 6 month old groups of ak and wt mice. Preproenkephalin levels in ak mice were elevated in both age groups. Drd1, 3 and 4 levels declined over time, in contrast to increasing Drd2 expression. Additional findings included decreased Chrnα6 expression and elevated VGluT1 expression at both time points in ak mice, and elevated AchE expression in young ak mice only. Results confirm that motor ability does not decline significantly for the first 6 months of life in ak mice. Their striatal gene expression patterns are consistent with dopaminergic denervation, and change over time, despite relatively unaltered motor performance.

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“…Present data do not allow any definitive conclusion regarding the mechanism behind the inhibitory action of clozapine on VTA DA neurons. Hypothetically, the effect could be mediated by (I) activation of presynaptic a7* nicotinic receptors located on glutamatergic afferents (McGehee et al, 1995;Wonnacott et al, 2000; leading to a potentially increased glutamate release by clozapine) (II) activation of postsynaptic a7* nicotinic receptor, located on cell soma or dendrites of VTA DA neurons or (III) displacement of KYNA at postsynaptic NMDA receptors located on cell soma or dendrites of GABAergic neurons projecting to VTA DA neurons, thereby restoring the balance between GABAergic and glutamatergic projections to the VTA. An interaction between clozapine and the a7* nicotinic receptor is supported by the demonstration of a clozapine-induced release of acetylcholine in the prefrontal cortex (Ichikawa et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Action of Clozapine on Rat Ventral Tegmental Area Dopamine Neurons Following Increased Levels of Endogenous Kynurenic Acid

Schwieler

Erhardt

2003

Neuropsychopharmacol

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The mode of action by which the atypical antipsychotic drug clozapine exerts its superior efficacy to ameliorate both positive and negative symptoms is still unknown. In the present in vivo electrophysiological study, we investigate the effects of haloperidol (a typical antipsychotic drug) and clozapine on ventral tegmental area (VTA) dopamine (DA) neurons in a situation of hyperdopaminergic activity in order to mimic tentatively a condition similar to that seen in schizophrenia. Increased DA transmission was induced by elevating endogenous levels of the N-methyl-D-aspartate receptor and a7* nicotinic receptor antagonist kynurenic acid (KYNA; by means of PNU 156561A, 40 mg /kg, i.v.). In control rats, i.v. administered haloperidol (0.05-0.8 mg/kg) or clozapine (1.25-10 mg/kg) was associated with increased firing rate and burst firing activity of VTA DA neurons. However, in rats displaying hyperdopaminergia (induced by elevated levels of KYNA), the effects of clozapine on VTA DA neurons were converted into pure inhibitory responses, including decrease in burst firing activity. In contrast, haloperidol still produced an excitatory action on VTA DA neurons in rats with elevated levels of endogenous brain KYNA. The results of the present study suggest that clozapine facilitates or inhibits VTA DA neurotransmission, depending on brain concentration of KYNA. Such an effect of clozapine may be related to its unique effect in also ameliorating negative symptoms of schizophrenia.

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Presynaptic nicotinic receptors modulating dopamine release in the rat striatum

Cited by 209 publications

References 28 publications

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

Motor deficits and altered striatal gene expression in aphakia (ak) mice

Inhibitory Action of Clozapine on Rat Ventral Tegmental Area Dopamine Neurons Following Increased Levels of Endogenous Kynurenic Acid

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