Enhanced nicotinic receptor function and drug abuse vulnerability.
- Authors
- Fagen, Zara M; Mitchum, Robert; Vezina, Paul; McGehee, Daniel S
- Year
- 2007
- Journal
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- PMID
- 17699659
- DOI
- 10.1523/JNEUROSCI.2017-06.2007
- PMCID
- PMC6672186
In animals and humans, vulnerability to drug abuse varies among individuals. Animals that display high activity levels in a novel environment are more likely to self-administer psychostimulant drugs, including nicotine, cocaine, amphetamine, and morphine. Recent reports from behavioral studies indicate that nicotinic acetylcholine receptor (nAChR) activity contributes to the rewarding effects of several different addictive drugs. Thus, we hypothesized that differences in nAChR activity may contribute to the predisposition to drug self-administration. After screening of adult rats (>60 d postnatal) for the behavioral response to a novel environment, electrophysiological measures of nAChR function were conducted in brain slices that included the mesoaccumbens dopamine neurons of the ventral tegmental area (VTA). We found a positive correlation between the response to novelty and nAChR function in each assay conducted, including nAChR modulation of glutamatergic and GABAergic synaptic inputs to VTA dopamine neurons, as well as somatic nAChR responses of VTA neurons. The response to novelty and sensitivity to addictive drugs are positively correlated with the hormonal response to stress. Consistent with this observation, we found enhanced nAChR responses in vitro after a 48 h corticosterone treatment and in vivo after 48 h of repeated stress. Each of these effects was inhibited by RU486 (11beta-[p-(dimethylamino)phenyl]-17beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one) pretreatment, suggesting a steroid hormone receptor-dependent process. These findings suggest that differences in nAChR function within the mesoaccumbens dopamine system may contribute to individual differences in drug abuse vulnerability and that these are likely attributable to differences in stress hormone levels.
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| Addictive drugs modify neurogenesis, synaptogenesis and synaptic plasticity to impair memory formation through neurotransmitter imbalances and signaling dysfunction. | Rezayof A et al. | β | 2023 | β |
| Allostatic load in opioid use disorder: a scoping review protocol. | Fan JQ et al. | β | 2023 | β |
| Dual use of e-cigarettes with conventional tobacco is associated with increased sleep latency in cross-sectional Study. | Advani I et al. | β | 2022 | β |
| Ξ±7 nicotinic acetylcholine receptor modulation of accumbal dopamine release covaries with novelty seeking. | Leach AC et al. | β | 2022 | β |
| Genome-wide association study of stimulant dependence. | Cox J et al. | β | 2021 | β |
| Nicotinic Antagonist UFR2709 Inhibits Nicotine Reward and Decreases Anxiety in Zebrafish. | Viscarra F et al. | β | 2020 | β |
| The modulatory role of nicotine on cognitive and non-cognitive functions. | Zarrindast MR et al. | β | 2019 | β |
| Adolescent Social Stress Increases Anxiety-like Behavior and Alters Synaptic Transmission, Without Influencing Nicotine Responses, in a Sex-Dependent Manner. | Caruso MJ et al. | β | 2018 | β |
| Ξ±6Ξ²2 subunit containing nicotinic acetylcholine receptors exert opposing actions on rapid dopamine signaling in the nucleus accumbens of rats with high-versus low-response to novelty. | Siciliano CA et al. | β | 2017 | β |
| Drugs currently in Phase II clinical trials for cocaine addiction. | Kim JH et al. | β | 2014 | β |
| Understanding counselors' implementation of tobacco cessation services with patients. | Eby LT et al. | β | 2014 | β |
| Acute restraint stress prevents nicotine-induced mesolimbic dopaminergic activation via a corticosterone-mediated mechanism: a microdialysis study in the rat. | Enrico P et al. | β | 2013 | β |
| Allostatic load as a tool for monitoring physiological dysregulations and comorbidities in patients with severe mental illnesses. | Bizik G et al. | β | 2013 | β |
| Intermittent nicotine exposure upregulates nAChRs in VTA dopamine neurons and sensitises locomotor responding to the drug. | Baker LK et al. | β | 2013 | β |
| Childhood adversity increases risk for nicotine dependence and interacts with Ξ±5 nicotinic acetylcholine receptor genotype specifically in males. | Xie P et al. | β | 2012 | β |
| Locomotor and stress responses to nicotine differ in adolescent and adult rats. | Cao J et al. | β | 2010 | β |
| Nicotinic receptors and stages of nicotine dependence. | Brennan KA et al. | β | 2010 | β |
| Ξ±7 and Ξ²2 nicotinic receptors control monoamine-mediated locomotor response. | VillΓ©gier AS et al. | β | 2010 | β |
| Adenylyl cyclase type 5 contributes to corticostriatal plasticity and striatum-dependent learning. | Kheirbek MA et al. | β | 2009 | β |
| Age matters. | McCutcheon JE et al. | β | 2009 | β |
| A virtual screening study of the acetylcholine binding protein using a relaxed-complex approach. | Babakhani A et al. | β | 2009 | β |
| Individual differences in response to novelty and the conditioned locomotor effects of nicotine. | Coolon RA et al. | β | 2009 | β |
| Maturation of excitatory synaptic transmission of the rat nucleus accumbens from juvenile to adult. | Kasanetz F et al. | β | 2009 | β |
| Molecular and cellular mechanisms of action of nicotine in the CNS. | Barik J et al. | β | 2009 | β |
| Stress-induced changes in nucleus accumbens glutamate synaptic plasticity. | Campioni MR et al. | β | 2009 | β |
| The impact of cigarette smoking on stimulant addiction. | Weinberger AH et al. | β | 2009 | β |
| Gates and filters: unveiling the physiological roles of nicotinic acetylcholine receptors in dopaminergic transmission. | Wonnacott S | β | 2008 | β |
| Long-term nicotine treatment differentially regulates striatal alpha6alpha4beta2* and alpha6(nonalpha4)beta2* nAChR expression and function. | Perez XA et al. | β | 2008 | β |
| Nicotinic acetylcholine receptors of the ventral tegmental area are involved in mediating morphine-state-dependent learning. | Rezayof A et al. | β | 2008 | β |
| Presynaptic opioid and nicotinic receptor modulation of dopamine overflow in the nucleus accumbens. | Britt JP et al. | β | 2008 | β |
| Exposure to nicotine and sensitization of nicotine-induced behaviors. | Vezina P et al. | β | 2007 | β |