Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures
Disturbances in the circadian rhythm alter the normal sleep-wake cycle, which increases vulnerability to drug abuse. Drug abuse can disrupt several homeostatic processes regulated by the circadian rhythm and influence addiction paradigms, including cravings for cocaine. The relationship between circ...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | Metabolites |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-1989/12/9/869 |
| _version_ | 1797484916233994240 |
|---|---|
| author | Mayur Doke Jay P. McLaughlin Hamid Baniasadi Thangavel Samikkannu |
| author_facet | Mayur Doke Jay P. McLaughlin Hamid Baniasadi Thangavel Samikkannu |
| author_sort | Mayur Doke |
| collection | DOAJ |
| description | Disturbances in the circadian rhythm alter the normal sleep-wake cycle, which increases vulnerability to drug abuse. Drug abuse can disrupt several homeostatic processes regulated by the circadian rhythm and influence addiction paradigms, including cravings for cocaine. The relationship between circadian rhythm and cocaine abuse is complex and bidirectional, and disruption impacts both brain function and metabolic profiles. Therefore, elucidating the impact of circadian rhythm changes and cocaine abuse on the human metabolome may provide new insights into identifying potential biomarkers. We examine the effect of cocaine administration with and without circadian rhythm sleep disruption (CRSD) on metabolite levels and compare these to healthy controls in an in vivo study. A metabolomics analysis is performed on the control, CRSD, cocaine, and CRSD with cocaine groups. Plasma metabolite concentrations are analyzed using a liquid chromatography electrochemical array platform. We identify 242 known metabolites compared to the control; 26 in the CRSD with cocaine group, 4 in the CRSD group, and 22 in the cocaine group are significantly differentially expressed. Intriguingly, in the CRSD with cocaine treatment group, the expression levels of uridine monophosphate (<i>p</i> < 0.008), adenosine 5′-diphosphate (<i>p</i> < 0.044), and inosine (<i>p</i> < 0.019) are significantly altered compared with those in the cocaine group. In summary, alterations in purine and pyrimidine metabolism provide clues regarding changes in the energy profile and metabolic pathways associated with chronic exposure to cocaine and CRSD. |
| first_indexed | 2024-03-09T23:11:17Z |
| format | Article |
| id | doaj.art-f2c1e064fce5471ca9f404a881cf75dc |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T23:11:17Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-f2c1e064fce5471ca9f404a881cf75dc2023-11-23T17:45:08ZengMDPI AGMetabolites2218-19892022-09-0112986910.3390/metabo12090869Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic SignaturesMayur Doke0Jay P. McLaughlin1Hamid Baniasadi2Thangavel Samikkannu3Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University Health Sciences Centers, College Station, TX 77843, USADepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL 32611, USADepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University Health Sciences Centers, College Station, TX 77843, USADisturbances in the circadian rhythm alter the normal sleep-wake cycle, which increases vulnerability to drug abuse. Drug abuse can disrupt several homeostatic processes regulated by the circadian rhythm and influence addiction paradigms, including cravings for cocaine. The relationship between circadian rhythm and cocaine abuse is complex and bidirectional, and disruption impacts both brain function and metabolic profiles. Therefore, elucidating the impact of circadian rhythm changes and cocaine abuse on the human metabolome may provide new insights into identifying potential biomarkers. We examine the effect of cocaine administration with and without circadian rhythm sleep disruption (CRSD) on metabolite levels and compare these to healthy controls in an in vivo study. A metabolomics analysis is performed on the control, CRSD, cocaine, and CRSD with cocaine groups. Plasma metabolite concentrations are analyzed using a liquid chromatography electrochemical array platform. We identify 242 known metabolites compared to the control; 26 in the CRSD with cocaine group, 4 in the CRSD group, and 22 in the cocaine group are significantly differentially expressed. Intriguingly, in the CRSD with cocaine treatment group, the expression levels of uridine monophosphate (<i>p</i> < 0.008), adenosine 5′-diphosphate (<i>p</i> < 0.044), and inosine (<i>p</i> < 0.019) are significantly altered compared with those in the cocaine group. In summary, alterations in purine and pyrimidine metabolism provide clues regarding changes in the energy profile and metabolic pathways associated with chronic exposure to cocaine and CRSD.https://www.mdpi.com/2218-1989/12/9/869circadian rhythmsleep disruptioncocaine abusemetabolismmetabolomicsbioinformatics |
| spellingShingle | Mayur Doke Jay P. McLaughlin Hamid Baniasadi Thangavel Samikkannu Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures Metabolites circadian rhythm sleep disruption cocaine abuse metabolism metabolomics bioinformatics |
| title | Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures |
| title_full | Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures |
| title_fullStr | Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures |
| title_full_unstemmed | Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures |
| title_short | Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures |
| title_sort | sleep disorder and cocaine abuse impact purine and pyrimidine nucleotide metabolic signatures |
| topic | circadian rhythm sleep disruption cocaine abuse metabolism metabolomics bioinformatics |
| url | https://www.mdpi.com/2218-1989/12/9/869 |
| work_keys_str_mv | AT mayurdoke sleepdisorderandcocaineabuseimpactpurineandpyrimidinenucleotidemetabolicsignatures AT jaypmclaughlin sleepdisorderandcocaineabuseimpactpurineandpyrimidinenucleotidemetabolicsignatures AT hamidbaniasadi sleepdisorderandcocaineabuseimpactpurineandpyrimidinenucleotidemetabolicsignatures AT thangavelsamikkannu sleepdisorderandcocaineabuseimpactpurineandpyrimidinenucleotidemetabolicsignatures |