Drug and alcohol dependence · 2026
Behavioral economic analysis of the reinforcing effects of fentanyl, cocaine, and mixtures of fentanyl and cocaine in rats.
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Vazquez Jacqueline M, Risca Harmony I, Collins Gregory T
Аннотация
BACKGROUND: The co-use of opioids, primarily fentanyl, and stimulants has resulted in substantial increases in fatal multi-drug overdoses, yet few studies have systematically investigated the reinforcing effects of fentanyl + stimulant mixtures. Behavioral economic demand curve analyses can quantify the relative value of drug reinforcers across different classes (e.g., opioids and stimulants), making it a valuable method to determine factors that promote polysubstance use.
METHODS: The current study used a multiple-component drug self-administration procedure to assess economic demand for fentanyl (0.00032-0.01mg/kg/inf), cocaine (0.032-1.0mg/kg/inf), and mixtures of fentanyl:cocaine at fixed-ratios of 10:1, 3:1, 1:1, 1:3, 1:10 (relative to the dose ranges used for each drug alone) in male and female Sprague-Dawley rats. Available unit doses of drug increased within-session across four components and response requirement (fixed-ratio; FR) increased across sessions. Demand curves for fentanyl, cocaine, and fentanyl:cocaine mixtures were generated, and elasticity coefficients (ɑ) estimated from demand curve analyses were used to assess the reinforcing value of the drugs alone and mixtures.
RESULTS: Demand for cocaine was more inelastic than demand for fentanyl (i.e., cocaine was a more valuable reinforcer); demand elasticity for the mixtures became more elastic as the proportion of fentanyl to cocaine increased, and more inelastic as the proportion of cocaine to fentanyl increased.
CONCLUSIONS: These findings suggest that interactions between the reinforcing effects of fentanyl and cocaine are additive in nature, however, it is unclear whether similar interactions would be observed under clinically relevant states, such as physical dependence on opioids or opioid withdrawal.
METHODS: The current study used a multiple-component drug self-administration procedure to assess economic demand for fentanyl (0.00032-0.01mg/kg/inf), cocaine (0.032-1.0mg/kg/inf), and mixtures of fentanyl:cocaine at fixed-ratios of 10:1, 3:1, 1:1, 1:3, 1:10 (relative to the dose ranges used for each drug alone) in male and female Sprague-Dawley rats. Available unit doses of drug increased within-session across four components and response requirement (fixed-ratio; FR) increased across sessions. Demand curves for fentanyl, cocaine, and fentanyl:cocaine mixtures were generated, and elasticity coefficients (ɑ) estimated from demand curve analyses were used to assess the reinforcing value of the drugs alone and mixtures.
RESULTS: Demand for cocaine was more inelastic than demand for fentanyl (i.e., cocaine was a more valuable reinforcer); demand elasticity for the mixtures became more elastic as the proportion of fentanyl to cocaine increased, and more inelastic as the proportion of cocaine to fentanyl increased.
CONCLUSIONS: These findings suggest that interactions between the reinforcing effects of fentanyl and cocaine are additive in nature, however, it is unclear whether similar interactions would be observed under clinically relevant states, such as physical dependence on opioids or opioid withdrawal.