Escalation and reinstatement of fentanyl self-administration in male and female rats.
Psychopharmacology (Berl)
; 238(8): 2261-2273, 2021 Aug.
Article
em En
| MEDLINE
| ID: mdl-33895852
ABSTRACT
RATIONALE Escalation of drug intake and craving are two DSM-5 hallmark symptoms of opioid use disorder (OUD). OBJECTIVES:
This study determined if escalation of intake as modeled by long access (LgA) self-administration (SA) and craving measured by reinstatement are related.METHODS:
Adult male and female Sprague-Dawley rats were trained to self-administer fentanyl across 7 daily 1-h short access (ShA) sessions, followed by 21 SA sessions of either 1- or 6-h duration (ShA or LgA). Following 14 1-h extinction sessions, Experiment 1 assessed reinstatement induced by either fentanyl (10 or 30 µg/kg) or yohimbine (1 or 2 mg/kg), and Experiment 2 assessed reinstatement induced by a drug-associated cue light.RESULTS:
Females acquired fentanyl SA faster than males. When shifted to LgA sessions, LgA rats escalated fentanyl intake, but ShA rats did not; no reliable sex difference in the rate of escalation was observed. In extinction, compared to ShA rats, LgA rats initially responded less and showed less decay of responding across sessions. A priming injection of fentanyl induced reinstatement, with LgA rats reinstating more than ShA rats at the 30 µg/kg dose. Yohimbine (1 mg/kg) also induced reinstatement, but there was no effect of access group or sex. With cue-induced reinstatement, LgA females reinstated less than LgA males and ShA females.CONCLUSION:
Among the different reinstatement tests assessed, escalation of fentanyl SA increased only drug-primed reinstatement, suggesting a limited relationship between escalation of drug intake and craving (reinstatement) for OUD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fentanila
/
Caracteres Sexuais
/
Condicionamento Operante
/
Fissura
/
Analgésicos Opioides
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Psychopharmacology (Berl)
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos