TY - JOUR

T1 - NMR-based Metabolomics and Fatty Acid Profiles to Unravel Biomarkers in Preclinical Animal Models of Compulsive Behavior

AU - Abreu, Ana C.

AU - Mora, Santiago

AU - Isabel Tristan, Ana

AU - Martin-Gonzalez, Elena

AU - Prados-Pardo, Angeles

AU - Moreno, Margarita

AU - Fernandez, Ignacio

PY - 2022

Y1 - 2022

N2 - Compulsivity is a key manifestation of inhibitory control deficit and a cardinal symptom of psychopathological conditions such as obsessive-compulsive and attention-deficit hyperactivity disorders, in which metabolic alterations have raised attention as putative biomarkers for early identification. The present study assessed the metabolic profile in a preclinical model of a compulsive phenotype of rats. We used the schedule-induced polydipsia (SIP) method to classify male Wistar rats into high drinkers (HDs) or low drinkers (LDs) according to their compulsive drinking rate developed by exposure to a fixed-time 60 s (FT-60) schedule of reinforcement with water available ad libitum during 20 sessions. Before and after SIP, blood samples were collected for subsequent serum analysis by nuclear magnetic resonance spectroscopy coupled to multivariate analysis. Although no differences existed in the pre-SIP set, the compulsive drinking behavior induced remarkable metabolic alterations: HD rats selected by SIP exhibited a hyperlipidemic, hypoglycemic, and hyperglutaminergic profile compared with their low-compulsive counterparts. Interestingly, these alterations were not attributable to the mere exposure to reward pellets because a control experiment did not show differences between HDs and LDs after 20 sessions of pellet consumption without intermittent reinforcement. Our results shed light toward the implication of dietary and metabolic factors underpinning the vulnerability to compulsive behaviors.

AB - Compulsivity is a key manifestation of inhibitory control deficit and a cardinal symptom of psychopathological conditions such as obsessive-compulsive and attention-deficit hyperactivity disorders, in which metabolic alterations have raised attention as putative biomarkers for early identification. The present study assessed the metabolic profile in a preclinical model of a compulsive phenotype of rats. We used the schedule-induced polydipsia (SIP) method to classify male Wistar rats into high drinkers (HDs) or low drinkers (LDs) according to their compulsive drinking rate developed by exposure to a fixed-time 60 s (FT-60) schedule of reinforcement with water available ad libitum during 20 sessions. Before and after SIP, blood samples were collected for subsequent serum analysis by nuclear magnetic resonance spectroscopy coupled to multivariate analysis. Although no differences existed in the pre-SIP set, the compulsive drinking behavior induced remarkable metabolic alterations: HD rats selected by SIP exhibited a hyperlipidemic, hypoglycemic, and hyperglutaminergic profile compared with their low-compulsive counterparts. Interestingly, these alterations were not attributable to the mere exposure to reward pellets because a control experiment did not show differences between HDs and LDs after 20 sessions of pellet consumption without intermittent reinforcement. Our results shed light toward the implication of dietary and metabolic factors underpinning the vulnerability to compulsive behaviors.

KW - compulsive behavior

KW - schedule-induced polydipsia

KW - biomarkers

KW - NMR

KW - metabolomics

KW - MAGNETIC-RESONANCE-SPECTROSCOPY

KW - SCHEDULE-INDUCED-POLYDIPSIA

KW - CHOLESTEROL LEVELS

KW - DISORDER

KW - IMPULSIVITY

KW - LEPTIN

KW - RATS

KW - DIET

U2 - 10.1021/acs.jproteome.1c00857

DO - 10.1021/acs.jproteome.1c00857

M3 - Journal article

C2 - 35142515

VL - 21

SP - 612

EP - 622

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 3

ER -