Effects of 5-HT2A receptor stimulation on economic demand for fentanyl after intermittent and continuous access self-administration in male rats

The relative value of and motivation for abused drugs often increases with drug experience and differs based on drug availability. Here, we determined how different intake patterns of fentanyl, a μ-opioid agonist, alter economic demand for fentanyl and how 5-HT_2A receptor stimulation affects economic demand for fentanyl. We used a within-session demand threshold procedure to characterize changes in economic demand for fentanyl before and after intermittent or continuous access schedules. We subsequently tested the acute effects of 5-HT_2A receptor stimulation with psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on economic demand for fentanyl. Extended fentanyl experience with both intermittent and continuous schedules increased fentanyl consumption at low cost (Q₀ ), increased total fentanyl consumption, and decreased demand elasticity (α), indicating both schedules elevated motivation to self-administer fentanyl. Overall, the two schedules produced similar alterations in economic demand for fentanyl, although low-cost consumption (Q₀ ) increased more in the continuous access group. Systemic injections of DOI (0.0-0.4 mg/kg, i.p.) dose-dependently produced economic demand changes in the opposite direction produced by fentanyl experience. DOI decreased motivation (increased "α"), decreased Q₀ , and decreased total fentanyl consumption. The selective 5-HT_2A antagonist, M100907 (0.3 mg/kg, i.p.), blocked the effects of DOI, indicating that DOI is acting through 5-HT_2A receptors to alter economic demand for fentanyl. In an economic food demand experiment, DOI (0.4 mg/kg) also increased demand elasticity and reduced food consumption. These results demonstrate that both intermittent and continuous fentanyl experience raise the economic demand for fentanyl, and acute 5-HT_2A receptor activation reduces economic demand for fentanyl and food.