Reinforcing effects of fentanyl analogs found in illicit drug markets.

Autor: Maitland AD; Designer Drug Research Unit (DDRU), National Institute on Drug Abuse (NIDA), Intramural Research Program (IRP), 333 Cassell Drive, Suite 4400, Baltimore, MD, 21224, USA., McGriff SA; Designer Drug Research Unit (DDRU), National Institute on Drug Abuse (NIDA), Intramural Research Program (IRP), 333 Cassell Drive, Suite 4400, Baltimore, MD, 21224, USA., Glatfelter GC; Designer Drug Research Unit (DDRU), National Institute on Drug Abuse (NIDA), Intramural Research Program (IRP), 333 Cassell Drive, Suite 4400, Baltimore, MD, 21224, USA., Schindler CW; Designer Drug Research Unit (DDRU), National Institute on Drug Abuse (NIDA), Intramural Research Program (IRP), 333 Cassell Drive, Suite 4400, Baltimore, MD, 21224, USA., Baumann MH; Designer Drug Research Unit (DDRU), National Institute on Drug Abuse (NIDA), Intramural Research Program (IRP), 333 Cassell Drive, Suite 4400, Baltimore, MD, 21224, USA. mbaumann@mail.nih.gov.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2024 Nov; Vol. 241 (11), pp. 2375-2383. Date of Electronic Publication: 2024 Jul 05.
DOI: 10.1007/s00213-024-06641-6
Abstrakt: Rationale: The potent synthetic opioid fentanyl, and its analogs, continue to drive opioid-related overdoses. Although the pharmacology of fentanyl is well characterized, there is little information about the reinforcing effects of clandestine fentanyl analogs (FAs).
Objectives: Here, we compared the effects of fentanyl and the FAs acetylfentanyl, butyrylfentanyl, and cyclopropylfentanyl on drug self-administration in male and female rats. These FAs feature chemical modifications at the carbonyl moiety of the fentanyl scaffold.
Methods: Sprague-Dawley rats fitted with intravenous jugular catheters were placed in chambers containing two nose poke holes. Active nose poke responses resulted in drug delivery (0.2 mL) over 2 s on a fixed-ratio 1 schedule, followed by a 20 s timeout. Acquisition doses were 0.01 mg/kg/inj for fentanyl and cyclopropylfentanyl, and 0.03 mg/kg/inj for acetylfentanyl and butyrylfentanyl. After 10 days of acquisition, dose-effect testing was carried out, followed by 10 days of saline extinction.
Results: Self-administration of fentanyl and FAs was acquired by both male and female rats, with no sex differences in acquisition rate. Fentanyl and FAs showed partial inverted-U dose-effect functions; cyclopropylfentanyl and fentanyl had similar potency, while acetylfentanyl and butyrylfentanyl were less potent. Maximal response rates were similar across drugs, with fentanyl and cyclopropylfentanyl showing maximum responding at 0.001 mg/kg/inj, acetylfentanyl at 0.01 mg/kg/inj, and butyrylfentanyl at 0.003 mg/kg/inj. No sex differences were detected for drug potency, efficacy, or rates of extinction.
Conclusions: Our work provides new evidence that FAs display significant abuse liability in male and female rats, which suggests the potential for compulsive use in humans.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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