Nicotinic and Dopaminergic Receptors
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چکیده
Although a predominant scientifi c theory exists on how nicotine leads to dependence, further study is needed to explore the relationships between genetic, environmental, and social infl uences on dependence. This concluding chapter summarizes how tobacco genetics may affect basic and clinical research and provides summaries and recommendations for each part of the monograph and cross-cutting recommendations for the entire volume.
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ACh/Dopamine Crosstalk in Motor Control and Reward: A Crucial Role for α6-Containing Nicotinic Receptors?
The midbrain dopaminergic system is a key element in the control of motor activity, cognition, and the motivational effects of drugs of abuse, including nicotine. In this issue of Neuron, Drenan et al. find that alpha6-containing nicotinic acetylcholine receptors might selectively activate mesolimbic and mesostriatal dopaminergic neurons, enhancing striatal dopamine release and its behavioral c...
متن کاملKnock-In Mice with Leu9’Ser 4 Nicotinic Receptors: Substantia Nigra Dopaminergic Neurons are Hypersensitive to Agonist and Lost Postnatally
This study analyzes the electrophysiological cause and behavioral consequence of dopaminergic cell loss in a knock-in mouse strain bearing hypersensitive nicotinic 4 receptor subunits (“L9’S mice”). Adult brains of L9’S mice show moderate loss of substantia nigra dopaminergic neurons and of striatal dopaminergic innervation. Amphetamine-stimulated locomotion is impaired, reflecting a reduction ...
متن کاملKnockin mice with Leu9'Ser alpha4-nicotinic receptors: substantia nigra dopaminergic neurons are hypersensitive to agonist and lost postnatally.
This study analyzes the electrophysiological cause and behavioral consequence of dopaminergic cell loss in a knockin mouse strain bearing hypersensitive nicotinic alpha4-receptor subunits ("L9'S mice"). Adult brains of L9'S mice show moderate loss of substantia nigra dopaminergic neurons and of striatal dopaminergic innervation. Amphetamine-stimulated locomotion is impaired, reflecting a reduct...
متن کاملPartial agonists for α4β2 nicotinic receptors stimulate dopaminergic neuron firing with relatively enhanced maximal effects.
BACKGROUND AND PURPOSE Partial agonists selective for α4β2 nicotinic ACh receptors have been developed for smoking cessation as they induce weak activation of native α4β2* receptors and inhibit effect of nicotine. However, it is unclear whether at brain functions there is an existence of receptor reserve that allows weak receptor activation to induce maximum physiological effects. We assessed t...
متن کاملSubcellular trafficking, pentameric assembly, and subunit stoichiometry of neuronal nicotinic acetylcholine receptors containing fluorescently labeled alpha6 and beta3 subunits.
Neuronal nicotinic acetylcholine (ACh) receptors are ligand-gated, cation-selective ion channels. Nicotinic receptors containing alpha4, alpha6, beta2, and beta3 subunits are expressed in midbrain dopaminergic neurons, and they are implicated in the response to smoked nicotine. Here, we have studied the cell biological and biophysical properties of receptors containing alpha6 and beta3 subunits...
متن کاملDivision of Pharmacology and Toxicology Department of Pharmacy University of Helsinki ROLE OF NICOTINIC ACETYLCHOLINE RECEPTORS IN CEREBRAL DOPAMINERGIC TRANSMISSION AND EXPRESSION OF FOS PROTEIN
Cigarette smoking is the most widespread form of drug abuse due to the addictive properties of nicotine present in tobacco. Via binding to specific receptors, known as nicotinic acetylcholine receptors (nAChRs), nicotine activates the mesolimbic dopamine (DA) system, which is hypothesised to be the final common pathway shared by rewarding stimuli in the brain. In addition to the mesolimbic dopa...
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