A buprenorphine-validated rat model of opioid use disorder optimized to study sex differences in vulnerability to relapse.

Abstract:

RATIONALE:Opioid use disorder (OUD) is a major epidemic in the USA. Despite evidence indicating that OUD may be particularly severe for women, preclinical models have yet to establish sex as a major factor in OUD. OBJECTIVES:Here, we examined sex differences in vulnerability to relapse following intermittent access fentanyl self-administration and protracted abstinence and used buprenorphine, the FDA-approved treatment for OUD, to test the validity of our model. METHODS:Following acquisition of fentanyl self-administration under one of two training conditions, male and female rats were given extended, 24-h/day access to fentanyl (0.25 μg/kg/infusion, 10 days) using an intermittent access procedure. Vulnerability to relapse was assessed using an extinction/cue-induced reinstatement procedure following 14 days of abstinence; buprenorphine (0 or 3 mg/kg/day) was administered throughout abstinence. RESULTS:Levels of drug-seeking were high following extended-access fentanyl self-administration and abstinence; buprenorphine markedly decreased drug-seeking supporting the validity of our relapse model. Females self-administered more fentanyl and responded at higher levels during subsequent extinction testing. Buprenorphine was effective in both sexes and eliminated sex and estrous phase differences in drug-seeking. Interestingly, the inclusion of a time-out during training had a major impact on later fentanyl self-administration in females, but not males, indicating that the initial exposure conditions can persistently impact vulnerability in females. CONCLUSIONS:These findings demonstrate the utility of this rat model for determining sex and hormonal influences on the development and treatment of OUD.

journal_title

Psychopharmacology

authors

Bakhti-Suroosh A,Towers EB,Lynch WJ

doi

10.1007/s00213-020-05750-2

subject

Has Abstract

pub_date

2021-01-06 00:00:00

eissn

0033-3158

issn

1432-2072

pii

10.1007/s00213-020-05750-2

pub_type

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