Autoradiographic evidence for nicotine receptors on nigrostriatal and mesolimbic dopaminergic neurons

Clarke, Paul B. S.; Pert, Agu

doi:10.1016/0006-8993(85)90456-1

Cited by 499 publications

(155 citation statements)

References 24 publications

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“…Studies of the reinforcing effects of self-administered intravenous nicotine on rodents have focused on the activation of nicotinic acetylcholine receptors (nAChRs) within the mesocorticocolimbic dopaminergic system, which projects from the VTA to the nucleus accumbens (NA) and the prefontal cortex (PFC) [15,16,17,18]. Anatomical studies suggest that VTA DA cells have high levels of nAChRs [19]. Nicotine affects the dopaminergic system through binding to the nAChR complexes [20], which activates then desensitizes these receptors.…”

Section: Biological Backgroundmentioning

confidence: 99%

A reduced model of DA neuronal dynamics that displays quiescence, tonic firing and bursting

Oster

Gutkin

2011

Journal of Physiology-Paris

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The dopaminergic (DA) neurons in the ventral tegmental area (VTA) project to the amygdyla, prefrontal cortex, and the ventral striatum, and are thought to signal reward prediction error. Numerous studies have focused on the tonic and phasic activity of the VTA DAergic neurons as encoding reward related signals. However, recent studies (e.g., [1]) suggest that bursting behavior specifically conveys reward-related information. Moreover, dopamine release during burst firing events is substantially greater than during regular spiking [2]. In addition, DAergic neuronal bursting is influenced by the nicotinic acetycholine receptors (nAChRs) [3,4]. Thus, understanding burst firing is essential when considering VTA neuronal dynamics. Here we introduce a single compartmental model of a VTA DA neuron. We demonstrate that this model captures the essential qualitative behavior of DAergic neuronal dynamics, yet is simple compared to existing, detailed, multi-compartmental models. Moreover, this model could be extended to include the detailed dynamics of two prevalent nAChR subtypes (α4β2 and α7), which is critical to elucidate the role that these receptors play in nicotine addiction.

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Section: Biological Backgroundmentioning

confidence: 99%

A reduced model of DA neuronal dynamics that displays quiescence, tonic firing and bursting

Oster

Gutkin

2011

Journal of Physiology-Paris

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“…Both muscarinic, particularly M 5 (Weiner et al, 1990), and nicotinic (Clarke and Pert, 1985) receptors provide input into VTA dopaminergic neurons (DANs). In turn, afferent DA projections from the VTA enervate the shell compartment of the NAc and activate ACh striatal interneurons, initiating the release of ACh.…”

Section: Mesostriatal Cholinergic Neuronsmentioning

confidence: 99%

The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

164

138

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Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.

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“…Nigrostriatal damage decreases high affinity nicotine binding sites that are thought to represent α4β2* nAChRs, while α7 nAChRs are unaffected [106,107]. Nigrostriatal damage also leads to dramatic declines in binding of 125 I-α-conotoxinMII [108], a ligand that identifies α6β2* in rodent striatum [80,109].…”

Section: Rodentsmentioning

confidence: 99%

Nicotinic receptors as CNS targets for Parkinson's disease

Quik

Bordia

O’Leary

2007

Biochemical Pharmacology

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Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal α6β2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, α4β2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to α6β2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics. Keywordsα-ConotoxinMII; Nicotine; Nicotinic; Parkinson's disease; Nigrostriatal; Striatum Parkinson's disease and the nicotinic cholinergic systemThe pathological hallmarks of Parkinson's disease are the presence of intracellular Lewy bodies and an extensive degeneration of the nigrostriatal dopaminergic system. [1][2][3][4]. There is a ≥70% decline in striatal dopamine and ≥50% loss of nigral dopaminergic neurons with the onset of clinical symptoms, which include bradykinesia, rigidity, and tremor [1][2][3][4].Although Parkinson's disease has primarily been considered a dopaminergic disorder, it is becoming increasingly clear that multiple CNS systems are involved in its pathogenesis [5][6][7]. Braak and coworkers have also identified Lewy bodies in numerous non-dopaminergic brain regions including the locus coeruleus, raphe nuclei, thalamus, amygdala, olfactory nuclei, pedunculopontine nucleus, and cerebral cortex [5,6]. These observations are in agreement with much earlier studies, which indicated that multiple CNS neuronal systems are affected in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the...

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Autoradiographic evidence for nicotine receptors on nigrostriatal and mesolimbic dopaminergic neurons

Cited by 499 publications

References 24 publications

A reduced model of DA neuronal dynamics that displays quiescence, tonic firing and bursting

A reduced model of DA neuronal dynamics that displays quiescence, tonic firing and bursting

The Role of Acetylcholine in Cocaine Addiction

Nicotinic receptors as CNS targets for Parkinson's disease

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