Effects of 5-HT2A Receptor Stimulation on Economic Demand for Fentanyl after Intermittent and Continuous Access Self-Administration in Male Rats
David Martin, Utsav Gyawali, Donna J. Calu
Addiction Biology May 26, 2020 DOI: 10.1111/adb.12926 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical behavioral pharmacology experiment (animal study) Peer reviewed |
|---|---|
| Population | Rats self-administering fentanyl or food |
| Interventions | Fentanyl 2 M100907 |
| Dose | DOI 0.0-0.4 mg/kg, i.p.; M100907 0.3 mg/kg, i.p. |
| Measures | within-session demand threshold procedure (economic demand: Q0, α, total consumption) |
| Topics | Serotonin |
| Key findings | Extended fentanyl self-administration under intermittent or continuous access increased economic demand for fentanyl (higher Q0, higher total consumption, lower α), suggesting elevated motivation. Acute DOI (0.0-0.4 mg/kg, i.p.) produced the opposite pattern, decreasing Q0 and total fentanyl consumption and increasing α; M100907 (0.3 mg/kg) blocked these effects, indicating 5-HT2A involvement. DOI (0.4 mg/kg) also increased food demand elasticity and reduced food consumption. |
Abstract
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‐HT2A 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‐HT2A 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‐HT2A antagonist, M100907 (0.3 mg/kg, i.p.), blocked the effects of DOI, indicating that DOI is acting through 5‐HT2A 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‐HT2A receptor activation reduces economic demand for fentanyl and food.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
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- μ-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges. Frontiers in Pharmacology 2023
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Cites 14
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials Journal of Psychopharmacology March 8, 2012
- The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act Neuropharmacology June 5, 2018
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