Inbred rat heredity and sex affect oral oxycodone self-administration and augmented intake in long sessions: correlations with anxiety and novelty-seeking.

Autor:	Sharp BM; Department of Genetics, Genomics and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163., Leng S; Department of Genetics, Genomics and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163., Huang J; Department of Pharmacology, Addiction Science and Toxicology, University of Tennessee Health Science Center, Memphis, Tennessee 38163., Jones C; Department of Genetics, Genomics and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163., Chen H; Department of Pharmacology, Addiction Science and Toxicology, University of Tennessee Health Science Center, Memphis, Tennessee 38163.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 May 29. Date of Electronic Publication: 2024 May 29.
DOI:	10.1101/2023.11.26.568753
Abstrakt:	Oxycodone abuse begins with prescription oral oxycodone, yet vulnerability factors determining abuse are largely undefined. We evaluated genetic vulnerability in a rat model of oral oxycodone self-administration (SA): increasing oxycodone concentration/session (0.025-0.1mg/ml; 1,4,16-h) followed by extinction and reinstatement. Active licks and oxycodone intake were greater in females than males during 4-h and 16-h sessions (p< 0.001). Each sex increased intake during 16-h vs 4-h sessions (p<2e-16), but a subset of strains dramatically augmented intake at 16-h (p=0.0005). Heritability ( h 2 ) of active licks/4-h at increasing oxycodone dose ranged from 0.30-0.53. Under a progressive ratio schedule, breakpoints were strain-dependent (p<2e-16). Cued reinstatement was greater in females (p<0.001). Naive rats were assessed by elevated plus maze (EPM), open field (OF) and novel object interaction (NOI). We correlated these behaviors with 28 parameters of oxycodone SA. Anxiety-defining EPM traits were most associated with SA in both sexes, whereas more OF and NOI traits were SA-associated in males. Sex and heredity are major determinants of motivation to take and seek oxycodone; intake augments dramatically during extended access in specific strains; and pleiotropic genes affect anxiety and multiple SA parameters. Competing Interests: Conflict of Interest Statement The authors declare that this study was supported exclusively by funds available from the National Institutes of Health (USA). No commercial funds were utilized and there were no competing interests.
Databáze:	MEDLINE
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