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 (p < 0.008),
adenosine 5′-diphosphate (p < 0.044), and
inosine (p < 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.