HIV-1 Tat Dysregulates the Hypothalamic-Pituitary-Adrenal Stress Axis and Potentiates Oxycodone-Mediated Psychomotor and Anxiety-Like Behavior of Male Mice
Abstract
:1. Introduction
2. Results
2.1. Experiment 1: HIV-1 Tat Expression Causes Adrenal Insufficiency and Potentiates Oxycodone’s Psychomotor Effects
2.2. Experiment 2: Repeated Exposure to Oxycodone Increases the Tat-Mediated Psychomotor and Glucocorticoid Stress Response
2.3. Experiment 3: Glucocorticoid and CRF Receptors Are Involved in the Psychomotor, Anxiety-Like, and HPA Axis Response to Oxycodone
2.4. Experiment 4: The Time-Course of HPA Axis Activation Was Influenced by Oxycodone Exposure
3. Discussion
4. Materials and Methods
4.1. Subjects and Housing
4.2. Chemicals
4.3. Procedure
4.3.1. Experiment 1: Assessment of Acute Oxycodone Exposure in Non-Stressed and Stressed Mice
4.3.2. Experiment 2: Assessment of Repeated Oxycodone Exposure in Non-Stressed and Stressed Mice
4.3.3. Experiment 3: Assessment of Acute Oxycodone Exposure Following GR and/or CRF-R Blockade
4.3.4. Experiment 4: Determination of Peak HPA Activation Following Tat or Oxycodone Exposure
4.4. Behavioral Assessment
4.4.1. Forced Swim Stress Stimulus
4.4.2. Open Field
4.4.3. Light-Dark Transition Test
4.5. Corticosterone Assay
4.5.1. Tissue Collection
4.5.2. Steroid Extraction
4.5.3. Enzyme-Linked Immunosorbant Assay (ELISA)
4.6. Statistical Analyses
Author Contributions
Funding
Conflicts of Interest
References
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Behavioral Measure | Non-Stressed | Stressed | ||||||
---|---|---|---|---|---|---|---|---|
Saline (0.9% w/v) | Oxycodone (3 mg/kg) | Saline (0.9% w/v) | Oxycodone (3 mg/kg) | |||||
Tat(−) (n = 8–9) | Tat(+) (n = 7–8) | Tat(−) (n = 12) | Tat(+) (n = 8–9) | Tat(−) (n = 8) | Tat(+) (n = 9) | Tat(−) (n = 8) | Tat(+) (n = 9) | |
Mean Velocity (m/s) | 0.025 ± 0.004 | 0.027 ± 0.002 * | 0.048 ± 0.008 † | 0.076 ± 0.009 †* | 0.005 ± 0.001 | 0.002 ± 0.001 | 0.012 ± 0.003 † | 0.015 ± 0.004 † |
Rearing number | 39.4 ± 6.2 | 23.8 ± 3.2 | 18.1 ± 11.4 † | 6.8 ± 2.2 † | 4.5 ± 2.4 | 0.9 ± 0.7 | 0.8 ± 0.3 | 0.7 ± 0.2 |
Rearing Time (s) | 31.13 ± 4.74 | 20.31 ± 2.58 * | 3.66 ± 1.56 † | 2.14 ± 0.92 †* | 2.61 ± 1.53 | 0.63 ± 0.60 | 0.29 ± 0.15 | 0.19 ± 0.09 |
Latency to first enter dark (s) | 61 ± 32 | 28 ± 19 | 14 ± 4 | 22 ± 9 | 77 ± 45 | 89 ± 36 | 63 ± 38 | 37 ± 33 |
Light zone time (s) | 106 ± 32 | 17 ± 5 * | 75 ± 17 | 43 ± 9 * | 102 ± 40 | 121 ± 27 | 112 ± 32 | 30 ± 5 |
Number of transitions | 9 ± 3 | 5 ± 1 * | 13 ± 2 | 8 ± 1 * | 9 ± 3 | 7 ± 1 | 13 ± 3 | 11 ± 3 |
Behavioral Measure | Non-Stressed | Stressed | ||||||
---|---|---|---|---|---|---|---|---|
Saline (0.9% w/v) | Oxycodone (3 mg/kg) | Saline (0.9% w/v) | Oxycodone (3 mg/kg) | |||||
Tat(−) (n = 8) | Tat(+) (n = 10) | Tat(−) (n = 8) | Tat(+) (n = 10) | Tat(−) (n = 8) | Tat(+) (n = 8) | Tat(−) (n = 8) | Tat(+) (n = 9) | |
Mean Velocity (m/s) | 0.022 ± 0.003 | 0.018 ± 0.003 | 0.077 ± 0.013 † | 0.089 ± 0.012 † | 0.007 ± 0.003 | 0.004 ± 0.001 | 0.01 ± 0.004 | 0.041 ± 0.011 § |
Rearing number | 34.8 ± 6.6 | 25.3 ± 6.2 | 13.8 ± 4.0 † | 19.7 ± 4.1 † | 1.1 ± 0.6 | 1.6 ± 0.5 | 1.4 ± 0.9 | 2.0 ± 1.2 |
Rearing Time (s) | 23.3 ± 5.6 | 19.5 ± 5.5 | 5.2 ± 1.8 † | 9.2 ± 2.3 † | 0.4 ± 0.3 | 0.6 ± 0.2 | 0.6 ± 0.5 | 1.0 ± 0.6 |
Latency to first enter dark (s) | 30 ± 12 | 81 ± 32 | 38 ± 17 | 8 ± 2 ‡ | 44 ± 37 | 38 ± 19 | 17 ± 9 | 14 ± 5 |
Light zone time (s) | 116 ± 32 | 91 ± 25 * | 119 ± 25 | 46 ± 12 * | 102± 38 | 68 ± 19 | 53 ± 12 † | 33± 7 † |
Number of transitions | 10 ± 2 | 9 ± 2 | 17 ± 3 † | 11 ± 1 † | 10 ± 2 | 11± 2 | 15 ± 3 | 11 ± 2 |
Behavioral Measure | Vehicle | Antalarmin | ||||||
Saline (0.9% w/v) | Oxycodone (3 mg/kg) | Saline (0.9% w/v) | Oxycodone (3 mg/kg) | |||||
Tat(−) (n = 8) | Tat(+) (n = 7–8) | Tat(−) (n = 8–9) | Tat(+) (n = 9) | Tat(−) (n = 8) | Tat(+) (n = 8–9) | Tat(−) (n = 8–9) | Tat(+) (n = 10) | |
Mean Velocity (m/s) | 0.031 ± 0.006 | 0.031 ± 0.005 | 0.053 ± 0.008 † | 0.11 ± 0.01 †* | 0.018 ± 0.003 | 0.016 ± 0.002 | 0.051 ± 0.007 † | 0.077 ± 0.005 †*# |
Rearing number | 34 ± 5 | 32 ± 8 | 8 ± 4 | 38 ± 12 | 16 ± 3 | 21 ± 6 | 10 ± 4 | 12 ± 5 |
Rearing Time (s) | 27.3 ± 4.5 | 27.7 ± 7.5 | 1.9 ± 0.7 † | 8.6 ± 2.0 † | 11 ± 2.4 # | 13.6 ± 4.5 # | 6.6 ± 3.3 † | 2.7 ± 0.9 † |
Latency to first entry to dark zone (s) | 40.7 ± 14.2 | 5.3 ± 1.8 | 10.7 ± 4.9 | 7.3 ± 1.7 | 86.9 ± 43.3 | 125.5 ± 36.4 | 7.0 ± 1.3 † | 6.8 ± 1.9 † |
Light zone time (s) | 177 ± 31 | 38 ± 11 * | 32. ± 7 † | 32 ± 5 | 104 ± 40 | 148 ± 34 # | 98 ± 31 | 74 ± 26 † |
Number of transitions | 14.9 ± 3.6 | 11.4 ± 2.9 | 8.4 ± 1.2 | 9.1 ± 1.3 | 6.0 ± 2.5 | 6.1 ± 1.3 | 14.2 ± 3.5 | 11.8 ± 2.3 |
RU-486 | Antalarmin + RU-486 | |||||||
Saline (0.9% w/v) | Oxycodone (3 mg/kg) | Saline (0.9% w/v) | Oxycodone (3 mg/kg) | |||||
Tat(−) (n = 8–9) | Tat(+) (n = 7–8) | Tat(−) (n = 8–9) | Tat(+) (n = 7–8) | Tat(−) (n = 9) | Tat(+) (n = 8) | Tat(−) (n = 9–10) | Tat(+) (n = 9–10) | |
Mean Velocity (m/s) | 0.01 ± 0.001 # | 0.021 ± 0.003 | 0.035 ± 0.006 † | 0.065 ± 0.011 †*# | 0.020 ± 0.003 | 0.018 ± 0.004 | 0.082 ± 0.012 †# | 0.075 ± 0.007 †# |
Rearing number | 9 ± 2 | 17 ± 4 | 25 ± 20 | 15 ± 7 | 12 ± 3 | 16 ± 5 | 57 ± 29 | 11 ± 4 |
Rearing Time (s) | 7.8 ± 2.1 # | 13.8 ± 3.5 # | 2.9 ± 1.9 † | 4.0 ± 1.2 † | 8.6 ± 1.9 # | 11.0 ± 4.0 # | 9.1 ± 2.9 † | 1.8 ± 0.4 † |
Latency to first entry to dark zone (s) | 78.0 ± 35.5 | 97.3 ± 52.4 | 16.1 ± 4.5 | 3.2 ± 0.7 | 110.0 ± 47.9 | 23.9 ± 6.4 | 14.8 ± 4.0 † | 3.8 ± 0.9 † |
Light zone time (s) | 120 ± 43 | 107 ± 43 | 116 ± 378 # | 8 ± 1 †* | 169 ± 40 | 34 ± 5 * | 200 ± 17 # | 61 ± 13 * |
Number of transitions | 3.4 ± 0.7 # | 3.1 ± 0.9 # | 9.0 ± 2.1 | 5.0 ± 0.9 | 7.4 ± 2.4 | 4.0 ± 0.5 | 27.4 ± 6.0 †# | 33.2 ± 15.5 †# |
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Salahuddin, M.F.; Mahdi, F.; Paris, J.J. HIV-1 Tat Dysregulates the Hypothalamic-Pituitary-Adrenal Stress Axis and Potentiates Oxycodone-Mediated Psychomotor and Anxiety-Like Behavior of Male Mice. Int. J. Mol. Sci. 2020, 21, 8212. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218212
Salahuddin MF, Mahdi F, Paris JJ. HIV-1 Tat Dysregulates the Hypothalamic-Pituitary-Adrenal Stress Axis and Potentiates Oxycodone-Mediated Psychomotor and Anxiety-Like Behavior of Male Mice. International Journal of Molecular Sciences. 2020; 21(21):8212. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218212
Chicago/Turabian StyleSalahuddin, Mohammed F., Fakhri Mahdi, and Jason J. Paris. 2020. "HIV-1 Tat Dysregulates the Hypothalamic-Pituitary-Adrenal Stress Axis and Potentiates Oxycodone-Mediated Psychomotor and Anxiety-Like Behavior of Male Mice" International Journal of Molecular Sciences 21, no. 21: 8212. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218212