title: Hedonic sensitivity to natural rewards is affected by prenatal stress in a sex-dependent manner.
abstract: Palatable food is a strong activator of the reward circuitry and may cause addictive behavior leading to eating disorders. How early life events and sex interact in shaping hedonic sensitivity to palatable food is largely unknown. We used prenatally restraint stressed (PRS) rats, which show abnormalities in the reward system and anxious/depressive-like behavior. Some of the hallmarks of PRS rats are known to be sex-dependent. We report that PRS enhanced and reduced milk chocolate-induced conditioned place preference in males and females, respectively. Male PRS rats also show increases in plasma dihydrotestosterone (DHT) levels and dopamine (DA) levels in the nucleus accumbens (NAc), and reductions in 5-hydroxytryptamine (5-HT) levels in the NAc and prefrontal cortex (PFC). In male rats, systemic treatment with the DHT-lowering drug finasteride reduced both milk chocolate preference and NAc DA levels. Female PRS rats showed lower plasma estradiol (E2) levels and lower DA levels in the NAc, and 5-HT levels in the NAc and PFC. E2supplementation reversed the reduction in milk chocolate preference and PFC 5-HT levels. In the hypothalamus, PRS increased ERα and ERβ estrogen receptor and CARTP (cocaine-and-amphetamine receptor transcript peptide) mRNA levels in males, and 5-HT2Creceptor mRNA levels in females. Changes were corrected by treatments with finasteride and E2, respectively. These new findings show that early life stress has a profound impact on hedonic sensitivity to high-palatable food via long-lasting changes in gonadal hormones. This paves the way to the development of hormonal strategies aimed at correcting abnormalities in the response to natural rewards.
authors.affiliation: International Associated Laboratory (LIA) 'Prenatal Stress and Neurodegenerative Diseases', UMR8576 University Lille 1/CNRS, France.|Sapienza University of Rome/IRCCS Neuromed, Italy.
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Reynaert
authors.affiliation: IRCCS, Centro Neurolesi 'Bonino-Pulejo', Italy.
authors.forename: Jordan
authors.initials: J
authors.lastname: Marrocco
authors.affiliation: International Associated Laboratory (LIA) 'Prenatal Stress and Neurodegenerative Diseases', UMR8576 University Lille 1/CNRS, France.|Sapienza University of Rome/IRCCS Neuromed, Italy.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mairesse
authors.affiliation: Advanced Molecular Diagnostic, Sant'Andrea Hospital, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Lionetto
authors.affiliation: Advanced Molecular Diagnostic, Sant'Andrea Hospital, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Simmaco
authors.affiliation: International Associated Laboratory (LIA) 'Prenatal Stress and Neurodegenerative Diseases', UMR8576 University Lille 1/CNRS, France.|Sapienza University of Rome/IRCCS Neuromed, Italy.
authors.forename: Lucie
authors.initials: L
authors.lastname: Deruyter
authors.affiliation: EA4483, University Lille 2, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Allorge
authors.affiliation: Institute of Neuroscience, National Research Council (CNR), Italy.|Genomnia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Moles
authors.affiliation: Department of Pharmacy, University of Genoa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pittaluga
authors.affiliation: International Associated Laboratory (LIA) 'Prenatal Stress and Neurodegenerative Diseases', UMR8576 University Lille 1/CNRS, France. stefania.maccari@univ-lille1.fr.|Sapienza University of Rome/IRCCS Neuromed, Italy. stefania.maccari@univ-lille1.fr.
authors.forename: Stefania
authors.initials: S
authors.lastname: Maccari
authors.affiliation: International Associated Laboratory (LIA) 'Prenatal Stress and Neurodegenerative Diseases', UMR8576 University Lille 1/CNRS, France.|Sapienza University of Rome/IRCCS Neuromed, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Morley-Fletcher
authors.affiliation: International Associated Laboratory (LIA) 'Prenatal Stress and Neurodegenerative Diseases', UMR8576 University Lille 1/CNRS, France.|Sapienza University of Rome/IRCCS Neuromed, Italy.
authors.forename: Gilles
authors.initials: G
authors.lastname: Van Camp
authors.affiliation: International Associated Laboratory (LIA) 'Prenatal Stress and Neurodegenerative Diseases', UMR8576 University Lille 1/CNRS, France.|Sapienza University of Rome/IRCCS Neuromed, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005260:Female; D018120:Finasteride / Q000494:pharmacology; D005518:Food Preferences / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000523:psychology; D012201:Reward; D012701:Serotonin / Q000378:metabolism; D012737:Sex Factors; D013315:Stress, Psychological / Q000523:psychology*
chemical_list: D015306:Biogenic Monoamines; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D012701:Serotonin; D018120:Finasteride; D004298:Dopamine
keywords: Animal model; conditioned place preference; early life stress; palatable food; sex hormones