Table 1.

Summary of recent findings on pharmacological interventions to attenuate fentanyl taking and seeking.

Drug	Route of administration	Pharmacological target	Subjects	Paradigm (fentanyl dose, model)	Main findings	References
SB-334867	IP	Orexin-1 receptor antagonist	Male Sprague-Dawley rats	Self-administration and behavioral economics procedure	SB-334867 decreases motivation for fentanyl without affecting drug consumption at null cost	Fragale et al. [69]
R121919	Intra-BNST injections	Corticotropin-releasing factor-1 receptor antagonist	Male Sprague-Dawley rats	2.5 mg/kg, infusion, self-administration	These patterns of responding with R121919 treatment result in less fentanyl-associated conditioned reinforcement during test	Gyawali et al. [71]
JMV2959	IP	Growth hormone secretagogue receptor antagonist	Male adult Wistar rats	20 or 30 μg/kg, SC; 10 μg/kg, IV	Pretreatment with JMV2959 significantly reduces the number of active lever presses and reduces fentanyl seeking/relapse-like behavior in rats on day 12 of forced abstinence	Sustkova-Fiserova et al. [64]
Methocinnamox	SC	μ-Opioid receptor antagonist	Male and female rhesus monkeys	0.00032 mg/kg, infusion, self-administration	Methocinnamox selectively reduces opioid self-administration and remains effective at times when its plasma levels are very low	Maguire et al. [97]
U50488 and nalfurafine	IV	κ-Opioid receptor agonists	Male and female Sprague-Dawley rats	0, 0.32–10 μg/kg, infusion, self-administration	Both U50488 and nalfurafine decrease fentanyl choice when administered contingently	Townsend [98]
PT150	IP	Glucocorticoid receptor antagonist	Male and female Sprague-Dawley rats	2.5 μg/kg, infusion, self-administration	Both footshock and yohimbine reinstate fentanyl-seeking; only footshock-induced reinstatement is decreased by PT150 (50 and 100 mg/kg)	Hammerslag et al. [103]
Levo-tetrahydropalmatine	IV	Dopamine receptor antagonist	Male C57BL/6 mice	0.05 mg/kg, conditioned place preference	Levo-tetrahydropalmatine suppresses the rewarding properties of fentanyl-induced conditioned place preference; the inhibitory effect may be related to the suppression of ERK and CREB phosphorylation in the hippocampus, nucleus accumbens, and prefrontal cortex in mice	Du et al. [99]
GEP44	SC	Novel dual agonist of glucagon-like peptide-1 receptors and neuropeptide Y Y2 receptors	Male Sprague-Dawley rats	2.5 μg/kg, self-administration	GEP44 attenuates opioid taking and seeking at a dose that does not suppress food intake or produce adverse malaise-like effects in fentanyl-experienced rats	Zhang et al. [101]
2,5-Dimethoxy-4-iodoamphetamine (DOI)	IP	Psychedelic 5-HT2A receptor agonist	Male Sprague-Dawley rats	2.5 μg/kg, injection, self-administration, intermittent and continuous schedules	DOI acts through 5-HT2A receptors to alter economic demand for fentanyl; in economic food demand experiments, DOI (0.4 mg/kg) increases demand elasticity and reduces food consumption	Martin et al. [100]
SB334867	IP	Orexin-1 receptor antagonist	Male Sprague-Dawley male rats	Intermittent self-administration	Addiction-like behaviors induced by intermittent access to fentanyl are reversed by SB-334867	Fragale et al. [68]

IP, intraperitoneal; SC, subcutaneous; IV, intravenous; BNST, bed nucleus of the stria terminalis.