Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3′-UTR of the <i>CHRNA</i>6 Gene
In human adolescents, a single nucleotide polymorphism (SNP), rs2304297, in the 3′-UTR of the nicotinic receptor subunit gene, <i>CHRNA</i>6, has been associated with increased smoking. To study the effects of the human <i>CHRNA6</i> 3′-UTR SNP, our lab generated knock-in rod...
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/6/3145 |
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| author | Anjelica Cardenas Yu Bai Yasamin Hajy Heydary Jiaqi Li Frances M. Leslie Shahrdad Lotfipour |
| author_facet | Anjelica Cardenas Yu Bai Yasamin Hajy Heydary Jiaqi Li Frances M. Leslie Shahrdad Lotfipour |
| author_sort | Anjelica Cardenas |
| collection | DOAJ |
| description | In human adolescents, a single nucleotide polymorphism (SNP), rs2304297, in the 3′-UTR of the nicotinic receptor subunit gene, <i>CHRNA</i>6, has been associated with increased smoking. To study the effects of the human <i>CHRNA6</i> 3′-UTR SNP, our lab generated knock-in rodent lines with either C or G SNP alleles. The objective of this study was to determine if the <i>CHRNA6</i> 3′-UTR SNP is functional in the knock-in rat lines. We hypothesized that the human <i>CHRNA6</i> 3′-UTR SNP knock-in does not impact baseline but enhances nicotine-induced behaviors. For baseline behaviors, rats underwent food self-administration at escalating schedules of reinforcement followed by a locomotor assay and a series of anxiety tests (postnatal day (PN) 25-39). In separate cohorts, adolescent rats underwent 1- or 4-day nicotine pretreatment (2×, 30 μg/kg/0.1 mL, i.v.). After the last nicotine injection (PN 31), animals were assessed behaviorally in an open-field chamber, and brain tissue was collected. We show the human <i>CHRNA6</i> 3′-UTR SNP knock-in does not affect food reinforcement, locomotor activity, or anxiety. Further, 4-day, but not 1-day, nicotine exposure enhances locomotion and anxiolytic behavior in a genotype- and sex-specific manner. These findings demonstrate that the human <i>CHRNA6</i> 3′-UTR SNP is functional in our in vivo model. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:42:29Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-75a4f9a996b540558cc867f1854e1cd02023-11-24T01:33:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236314510.3390/ijms23063145Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3′-UTR of the <i>CHRNA</i>6 GeneAnjelica Cardenas0Yu Bai1Yasamin Hajy Heydary2Jiaqi Li3Frances M. Leslie4Shahrdad Lotfipour5Department of Pharmaceutical Sciences, College of Health Sciences, University of California, Irvine, CA 92697, USADepartment of Biological Sciences, University of California, Irvine, CA 92697, USADepartment of Pharmaceutical Sciences, College of Health Sciences, University of California, Irvine, CA 92697, USADepartment of Biological Sciences, University of California, Irvine, CA 92697, USADepartment of Pharmaceutical Sciences, College of Health Sciences, University of California, Irvine, CA 92697, USADepartment of Pharmaceutical Sciences, College of Health Sciences, University of California, Irvine, CA 92697, USAIn human adolescents, a single nucleotide polymorphism (SNP), rs2304297, in the 3′-UTR of the nicotinic receptor subunit gene, <i>CHRNA</i>6, has been associated with increased smoking. To study the effects of the human <i>CHRNA6</i> 3′-UTR SNP, our lab generated knock-in rodent lines with either C or G SNP alleles. The objective of this study was to determine if the <i>CHRNA6</i> 3′-UTR SNP is functional in the knock-in rat lines. We hypothesized that the human <i>CHRNA6</i> 3′-UTR SNP knock-in does not impact baseline but enhances nicotine-induced behaviors. For baseline behaviors, rats underwent food self-administration at escalating schedules of reinforcement followed by a locomotor assay and a series of anxiety tests (postnatal day (PN) 25-39). In separate cohorts, adolescent rats underwent 1- or 4-day nicotine pretreatment (2×, 30 μg/kg/0.1 mL, i.v.). After the last nicotine injection (PN 31), animals were assessed behaviorally in an open-field chamber, and brain tissue was collected. We show the human <i>CHRNA6</i> 3′-UTR SNP knock-in does not affect food reinforcement, locomotor activity, or anxiety. Further, 4-day, but not 1-day, nicotine exposure enhances locomotion and anxiolytic behavior in a genotype- and sex-specific manner. These findings demonstrate that the human <i>CHRNA6</i> 3′-UTR SNP is functional in our in vivo model.https://www.mdpi.com/1422-0067/23/6/3145<i>CHRNA6</i>locomotor activityanxiety-like behavioradolescentpharmacogenetics |
| spellingShingle | Anjelica Cardenas Yu Bai Yasamin Hajy Heydary Jiaqi Li Frances M. Leslie Shahrdad Lotfipour Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3′-UTR of the <i>CHRNA</i>6 Gene International Journal of Molecular Sciences <i>CHRNA6</i> locomotor activity anxiety-like behavior adolescent pharmacogenetics |
| title | Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3′-UTR of the <i>CHRNA</i>6 Gene |
| title_full | Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3′-UTR of the <i>CHRNA</i>6 Gene |
| title_fullStr | Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3′-UTR of the <i>CHRNA</i>6 Gene |
| title_full_unstemmed | Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3′-UTR of the <i>CHRNA</i>6 Gene |
| title_short | Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3′-UTR of the <i>CHRNA</i>6 Gene |
| title_sort | sex and genotype dependent nicotine induced behaviors in adolescent rats with a human polymorphism rs2304297 in the 3 utr of the i chrna i 6 gene |
| topic | <i>CHRNA6</i> locomotor activity anxiety-like behavior adolescent pharmacogenetics |
| url | https://www.mdpi.com/1422-0067/23/6/3145 |
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