Effects of exposure to chronic uncertainty and a sensitizing regimen of amphetamine injections on locomotion, decision-making, and dopamine receptors in rats
| العنوان: | Effects of exposure to chronic uncertainty and a sensitizing regimen of amphetamine injections on locomotion, decision-making, and dopamine receptors in rats |
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| المؤلفون: | Fiona D. Zeeb, Paul J. Fletcher, Victoria Fugariu, José N. Nobrega, Martin Zack |
| المصدر: | Neuropsychopharmacology |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Dextroamphetamine, Decision Making, Article, Receptors, Dopamine, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, Risk-Taking, 0302 clinical medicine, Dopamine Uptake Inhibitors, Reward, Dopamine receptor D3, Dopamine, Dopamine receptor D2, Internal medicine, Conditioning, Psychological, medicine, Animals, Amphetamine, Saccharin, Sensitization, Pharmacology, business.industry, Uncertainty, Classical conditioning, Corpus Striatum, 030227 psychiatry, Psychiatry and Mental health, Endocrinology, medicine.anatomical_structure, chemistry, Dopamine receptor, Gambling, business, Locomotion, 030217 neurology & neurosurgery, medicine.drug |
| الوصف: | Gambling disorder (GD) is a behavioral addiction that may be linked to alterations in dopamine (DA) systems. Gambling involves chronic exposure to uncertain reward, which can sensitize the activity of DA systems. Here we explored how combinations of Pavlovian and instrumental uncertainty impact DA sensitization and risky decision-making. Experiment 1: 40 rats underwent 66 uncertainty exposure (UE) sessions during which they responded for saccharin. Animal responding was reinforced according to a fixed or variable (FR/VR) ratio schedule that turned on a conditioned stimulus (CS; light), which predicted saccharin on 50% or 100% of trials. Animals responded under one of the four conditions: FR-CS100% (no uncertainty), VR-CS100%, FR-CS50%, and VR-CS50% (maximal uncertainty). DA sensitization was inferred from an enhanced locomotor response to d-amphetamine (d-AMPH; 0.5 mg/kg) challenge. The rat gambling task (rGT) was used to assess decision-making. Experiment 2: 24 rats received 5 weeks of sensitizing d-AMPH or saline doses, followed by locomotor activity and rGT testing. Experiment 3: Effects of UE and a sensitizing d-AMPH regimen on DA D1, D2, and D3 receptor binding were assessed in 44 rats using autoradiography. Compared to FR-CS100%, VR-CS100% and VR-CS50% rats displayed a greater locomotor response to d-AMPH, and VR-CS50% rats demonstrated riskier decision-making. Chronic d-AMPH-treated rats mirrored the effects of VR-CS50% groups on these two indices. Both VR-CS50% and d-AMPH-treated groups had increased striatal DA D2 receptor binding. These results suggest that chronic uncertainty exposure, similar to exposure to a sensitizing d-AMPH regimen, sensitized the function of DA systems and increased risky decision-making. |
| تدمد: | 1740-634X 0893-133X |
| DOI: | 10.1038/s41386-020-0599-x |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5d09d1716942c6f6b554ff600cac01a0 https://doi.org/10.1038/s41386-020-0599-x |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5d09d1716942c6f6b554ff600cac01a0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1740634X 0893133X |
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| DOI: | 10.1038/s41386-020-0599-x |