Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine
NaturePublished 1 January 1998
Marina R. Picciotto, Michèle Zoli, Roberto Rimondini, Clément Léna, Lisa M. Marubio, Emilio Merlo Pich
Citations1,327
SJR quartileQ1
SJR score18.29
SNIP10.16
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The results strongly support the idea that the β2-containing neuronal nicotinic acetylcholine receptor is involved in mediating the reinforcing properties of nicotine.
Abstract
Release of the neurotransmitter dopamine in the mesolimbic system of the brain mediates the reinforcing properties of several drugs of abuse, including nicotine. Here we investigate the contribution of the high-affinity neuronal nicotinic acetylcholine receptor to the effects of nicotine on the mesolimbic dopamine system in mice lacking the beta2 subunit of this receptor. We found that nicotine stimulates dopamine release in the ventral striatum of wild-type mice but not in the ventral striatum of beta2-mutant mice. Using patch-clamp recording, we show that mesencephalic dopaminergic neurons from mice without the beta2 subunit no longer respond to nicotine, and that self-administration of nicotine is attenuated in these mutant mice. Our results strongly support the idea that the beta2-containing neuronal nicotinic acetylcholine receptor is involved in mediating the reinforcing properties of nicotine.
Keywords
NeuroscienceBiochemistry, Genetics and Molecular Biology
Trends in Pharmacological SciencesDrugs of abuse: anatomy, pharmacology and function of reward pathways
2,084 Citations1992George F. Koob
The results suggest that brain reward systems have a multidetermined neuropharmacological basis that may involve some common neuroanatomical elements.
NatureEffects of nicotine on the nucleus accumbens and similarity to those of addictive drugs
1,081 Citations1996Francesco E. Pontieri, Gianluigi Tanda +2 more
It is reported that intravenous nicotine in the rat, at doses known to maintain self-administration, stimulates local energy metabolism, as measured by 2-deoxyglucose autoradiography, and dopamine transmission, as estimated by brain microdialysis, in the shell of the nucleus accumbens.
ScienceNicotine Enhancement of Fast Excitatory Synaptic Transmission in CNS by Presynaptic Receptors
1,077 Citations1995Daniel S. McGehee, Mark J.S. Heath +3 more
Findings reveal that CNS nAChRs enhance fast excitatory transmission, providing a likely mechanism for the complex behavioral effects of nicotine.
PsychopharmacologyThe mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine
832 Citations1992William A. Corrigall, Keith B.J. Franklin +2 more
The data demonstrate that the reinforcing effects of nicotine occur within the central nervous system, and that the mesolimbic dopamine projection plays an important role in these effects.
NeuronNicotinic Receptors in the Development and Modulation of CNS Synapses
774 Citations1996Lorna W. Role, Darwin K. Berg
This work presents a new approach to evaluating the role of tobacco smoke in the development of Duchenne muscular dystrophy and suggests that smokeless tobacco may be a more effective treatment than traditional chemotherapy.
Journal of NeuroscienceMorphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro
726 Citations1989AA Grace, SP Onn
Spontaneously firing DA cells recorded in vitro had a number of distinguishing electrophysiological characteristics in common with those of DA neurons recorded in vivo, such as the presence of a slow depolarizing potential driving spike activity and a characteristic depolarized spike threshold.
NatureAbnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain
664 Citations1995Marina R. Picciotto, Michèle Zoli +8 more
It is reported here that high-affinity binding sites for nicotine are absent from the brains of mice homozygous for the β2-subunit mutation, and electrophysiological recording from brain slices reveals that thalamic neurons from these mice do not respond to nicotine application.
NeuronMolecular and Cellular Aspects of Nicotine Abuse
610 Citations1996John A. Dani, Steve Heinemann
There may be long-term synaptic changes that result in the learned behaviors that are associated with smoking and with the context in which smoking takes place that contribute to the difficulty in breaking the nicotine habit.
Journal of NeuroscienceBoth alpha- and beta-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors
560 Citations1991CW Luetje, James W. Patrick
The oocyte system can accurately express ligand-gated ion channels because mouse muscle nAChRs expressed in oocytes display pharmacological properties similar to those reported for these receptors expressed on BC3H-1 cells.
SynapseSystemic nicotine‐induced dopamine release in the rat nucleus accumbens is regulated by nicotinic receptors in the ventral tegmental area
520 Citations1994Magnus Nisell, George G. Nomikos +1 more
The results suggest that nicotinic receptors in the somatodendritic region may be of greater importance than those located in the terminal area for the stimulatory action of systemic NIC on the mesolimbic DA system and support the notion that the meslimbic dopaminergic system is phasically rather than tonically regulated by nicotinics receptor activation within the VTA.
Journal of NeuroscienceLocalization of dopamine D2 receptor mRNA and D1 and D2 receptor binding in the rat brain and pituitary: an in situ hybridization- receptor autoradiographic analysis
463 Citations1990Alfred Mansour, Meador-Woodruff Jh +4 more
Analysis of adjacent tissue sections in which receptor autoradiography and in situ hybridization had been performed revealed several brain regions where the D2 binding site and corresponding mRNA appear to be similarly distributed, including the caudate-putamen, nucleus accumbens, olfactory tubercle, globus pallidus, substantia nigra, and ventral tegmental area.
European Journal of NeuroscienceNeuronal Nicotinic Receptor a6 Subunit mRNA is Selectively Concentrated in Catecholaminergic Nuclei of the Rat Brain
388 Citations1996Nicolas Le Novère, Michèle Zoli +1 more
The present results show that a6 is the major nicotinic acetylcholine receptor a subunit expressed in dopaminergic cell groups of the mesencephalon and noradrenergic cells of the locus coeruleus, suggesting the involvement of the a6 subunit in some of the major functions of central Nicotinic circuits, including the modulation of locomotor behaviour and reward.
Journal of NeurochemistryCharacterization of Nicotinic Receptor‐Mediated [<sup>3</sup>H]Dopamine Release from Synaptosomes Prepared from Mouse Striatum
350 Citations1992Sharon R. Grady, Michael J. Marks +2 more
It is established that presynaptic nicotinic receptors modulate dopamine release in the mouse striatum, and this finding suggests either that more than one Nicotinic receptor regulates dopamine release or that not all agonists interact with the same receptor in an identical fashion.
ScienceCommon Neural Substrates for the Addictive Properties of Nicotine and Cocaine
343 Citations1997Emilio Merlo Pich, Sonia Pagliusi +4 more
The reinforcing properties of cocaine and nicotine map on selected structures of the terminal fields of the mesocorticolimbic dopamine system, supporting the idea that common substrates for these addictive drugs exist.
Journal of NeuroscienceD-1 dopamine receptors in the rat brain: a quantitative autoradiographic analysis
340 Citations1986T. Renee Dawson, DR Gehlert +3 more
The distribution of dopamine D-1 receptors has been determined in the rat brain by a quantitative in vitro light-microscopic autoradiographic method and the results suggest possible CNS sites of action of D- 1 dopamine receptor selective compounds.
Journal of Pharmacology and Experimental TherapeuticsEvidence that mesolimbic dopaminergic activation underlies the locomotor stimulant action of nicotine in rats.
319 Citations1988Paul B. S. Clarke, Davina S. Fu +2 more
In rats which have been chronically treated with l-nicotine, a selective activation of mesolimbic dopamine appears to mediate the locomotor stimulant effect of this drug.
British Journal of PharmacologyNicotinic excitation of rat ventral tegmental neurones <i>in vitro</i> studied by intracellular recording
287 Citations1989Paolo Calabresi, M.G. Lacey +1 more
Responses to ACh and nicotine resemble those previously described on autonomic ganglion cells and may contribute to the positive reinforcement associated with nicotine consumption in rat brain slices.
Journal of NeuroscienceModulation of dopamine efflux in the nucleus accumbens after cholinergic stimulation of the ventral tegmental area in intact, pedunculopontine tegmental nucleus-lesioned, and laterodorsal tegmental nucleus-lesioned rats
213 Citations1996Charles D. Blaha, LF Allen +5 more
The present data show that cholinergic neurons in the LDTg, but not the PPTg, regulate the activity of DA-containing neuron in the VTA, which complements previous data showing that cholinesterase inhibitors in the PTTg regulate DA- containing neurons inThe SNc.
Life SciencesA rapid and sensitive assay for tyrosine-3-monooxygenase based upon the release of 3H2O and adsorption of [3H]-tyrosine by charcoal
202 Citations1986John F. Reinhard, Gary K. Smith +1 more
A rapid, simple and sensitive assay has been developed for tyrosine-3-monooxygenase, the enzyme catalyzing the rate-limiting step in catecholamine biosynthesis.
Pharmacology Biochemistry and BehaviorCigarette smokers self-administer intravenous nicotine
157 Citations1983Jack E. Henningfield, Katsumasa Miyasato +1 more
Human volunteers who smoked cigarettes were given the opportunity to press a lever that resulted in intravenous injections of saline or nicotine, and reported that nicotine produced subjective effects similar to those produced by administration of abuse drugs such as morphine or cocaine.
NeuropharmacologyBehavioural and pharmacokinetic studies on nicotine, cytisine and lobeline
141 Citations1990C. Reavill, Bernard Walther +2 more
In vivo tests showed that the behavioural effects of cytisine and lobeline cannot be correlated with their effects at the binding site for tritiated nicotine, and since pharmacokinetic factors do not account for this discrepancy, a pharmacodynamic explanation will be necessary.
Pharmacology Biochemistry and BehaviorNicotine-induced conditioned place preference and conditioned place aversion in mice
139 Citations1995Fred O. Risinger, Roger A. Oakes
It is indicated that nicotine has dose-dependent rewarding and aversive effects measured in an unbiased place conditioning paradigm using mice, with nicotine-induced conditioned place preference and conditioned place aversion being noted.
Journal of NeurochemistryNicotine Indirectly Inhibits [<sup>3</sup>H]Dopamine Uptake at Concentrations That Do Not Directly Promote [<sup>3</sup>H]Dopamine Release in Rat Striatum
73 Citations1991Sari Izenwasser, Henry M. Jacocks +2 more
The effect of nicotine on dopamine uptake appears to be mediated by a receptor similar to the nicotinic acetylcholine receptor, however, these receptors do not seem to be on the terminals that are accumulating dopamine, since tetrodotoxin prevented the effect of Nicotine on [3H]dopamine uptake.
Journal of NeurochemistryDopaminergic Inhibition of Prolactin Release and Calcium Influx Induced by Neurotensin in Anterior Pituitary Is Independent of Cyclic AMP System
68 Citations1986Maurizio Memo, Laura Castelletti +4 more
The lack of effect of low concentrations of DA on both basal adenylate cyclase activity and cyclic AMP content in pituitary cells, together with their capacity to inhibit the NT effects in pertussis toxin‐treated cells, suggest that DA may act independently of cyclicAMP in the control of PRL secretion.
SynapseDistribution of cocaine recognition sites in monkey brain: I. In vitro autoradiography with [<sup>3</sup>H]CFT
60 Citations1991Marc J. Kaufman, Roger D. Spealman +1 more
The results demonstrate that although densities of [3H]CFT binding sites are highest in the caudate nucleus, putamen, and nucleus accumbens/olfactory tubercle, significant levels of binding can be detected in other brain regions that may contribute to the behavioral and physiological effects of cocaine.
Pharmacology Biochemistry and BehaviorIntravenous cocaine self-administration in the C57BL/6J mouse
43 Citations1995Nicholas J. Grahame, Tamara J. Phillips +2 more
These findings support the feasibility of using intravenous self-administration to assess reinforcement in genetically well-defined populations and offer strong evidence of cocaine-directed behavior in the C57BL/6 inbred mouse strain.
PsychopharmacologyNicotine reinforcement in rats with histories of cocaine self-administration
41 Citations1995Michela Tessari, Enzo Valerio +2 more
Results indicate that nicotine can serve as a positive reinforcer for rats under the historical and schedule conditions described and suggest that nicotine self-administration occurs in rats.
Neuroscience LettersPEC-60 increases dopamine but not GABA release in the dorsolateral neostriatum of the halothane anaesthetized rat. An in vivo microdialysis study
7 Citations1994Roberto Rimondini, William T. O’Connor +6 more
The data suggest that PEC-60 plays a role in modulating striatal DA release but not DA metabolism and that this effect is primarily targeted on the presynaptic DA terminals of the nigrostriatal DA pathway rather than on the postsynaptic striatopallidal GABA projection neurons in the dorsolateral striatum.