Evaluation of potential punishing effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in rhesus monkeys responding under a choice procedure

• Published in: Behavioural pharmacology Vol. 35; no. 7; p. 378
• Main Author: Maguire, David R
• Format: Journal Article
• Language: English
• Published: England 01.10.2024
• Subjects: Animals; Choice Behavior - drug effects; Conditioning, Operant - drug effects; DOM 2,5-Dimethoxy-4-Methylamphetamine - pharmacology; Dose-Response Relationship, Drug; Female; Fentanyl - pharmacology; Histamine - pharmacology; Macaca mulatta; Male; Punishment; Reinforcement, Psychology; Serotonin 5-HT2 Receptor Agonists - pharmacology
• DOI: 10.1097/FBP.0000000000000787

There has been substantial and growing interest in the therapeutic utility of drugs acting at serotonin 2A subtype (5-HT 2A ) receptors, increasing the need for characterization of potential beneficial and adverse effects of such compounds. Although numerous studies have evaluated the possible rewarding and reinforcing effects of 5-HT 2A receptor agonists, there have been relatively few studies on potential aversive effects. The current study investigated punishing effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in four rhesus monkeys responding under a choice procedure in which responding on one lever delivered a sucrose pellet alone and responding on the other lever delivered a sucrose pellet plus an intravenous infusion of a range of doses of fentanyl (0.1-3.2 µg/kg/infusion), histamine (3.2-100 µg/kg/infusion), or DOM (3.2-100 µg/kg/infusion). When fentanyl was available, responding for a pellet plus an infusion increased dose dependently in all subjects, indicating a positive reinforcing effect of fentanyl. When histamine was available, responding for a pellet plus an infusion decreased in three of four subjects, indicating a punishing effect of histamine. Whether available before or after histamine, DOM did not systematically alter choice across the range of doses tested. These results suggest that the 5-HT 2A receptor agonist DOM has neither positive reinforcing nor punishing effects under a choice procedure that is sensitive to both processes.