Oxycodone-like discriminative stimulus effects of fentanyl-related emerging drugs of abuse in mice
| Autor: | D. Matthew Walentiny, Patrick M. Beardsley, Lea T. Moisa |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Narcotics 0301 basic medicine Pharmacology Generalization Psychological Naltrexone Fentanyl Discrimination Learning Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Piperidines medicine Animals Ocfentanil Furans business.industry Opioid overdose medicine.disease 030104 developmental biology Opioid μ-opioid receptor business Stimulus control Oxycodone 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuropharmacology. 150:210-216 |
| ISSN: | 0028-3908 |
| Popis: | Background Fentanyl and its structurally related compounds have emerged as the most significant contributors to opioid overdose fatalities in recent years. While there is abundant information about the pharmacological effects of fentanyl, far less is known of its more recently abused analogs. The objective of this study was to determine whether fentanyl and several fentanyl-related substances would engender oxycodone-like responding in a mouse model of oxycodone discrimination. Oxycodone was selected as the training drug due to its high selectivity for mu opioid receptors. Compounds that elicited oxycodone-like responding in this procedure would likely evoke overlapping subjective experiences. Methods Adult male C57BL/6 mice were trained to discriminate 1.3 mg/kg oxycodone from vehicle in a food-reinforced, two-lever choice procedure. Generalization tests were conducted with fentanyl and the following fentanyl-related compounds: ocfentanil, 3-furanyl fentanyl, crotonylfentanyl, and valerylfentanyl. Results Fentanyl and each of its analogs completely generalized to the 1.3 mg/kg oxycodone discriminative stimulus and naltrexone pretreatment significantly decreased oxycodone-like responding for each compound. Rank order potency for engendering oxycodone-appropriate responding was ocfentanil > fentanyl > 3-furanyl fentanyl ≈ crotonylfentanyl > oxycodone > valerylfentanyl. Drug doses that evoked full substitution also significantly suppressed response rates compared to vehicle. Conclusions These results indicate that the discriminative stimulus, and by extension, the interoceptive and subjective effects of the tested fentanyl analogs, overlap with those of oxycodone. These observations consequentially support the prediction that they would also engender the likelihood for abuse similar to oxycodone. This article is part of the Special Issue entitled ‘New Vistas in Opioid Pharmacology’. |
| Databáze: | OpenAIRE |
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