The effects of chronic semaglutide (OzempicTM) administration on cue- and drug-induced reinstatement of cocaine-seeking behavior in rats

Grant Ghaly

Research Mentor: Shelly Flagel
Mentor Department: Psychiatry/MBNI, Medicine
Author(s): Grant Ghaly, Christopher Turner, Shelly Flagel
Session: Session 2 (10:00 AM – 10:50 AM)
Presentation Type: Poster 81

Abstract

Glucagon like peptide-1 receptor agonists (GLP-1RAs), like semaglutide, promote weight loss by suppressing appetite and potentially reducing “food noise”–intrusive thoughts about food. Neural pathways underlying food motivation overlap with those for drugs of abuse, suggesting semaglutide’s effects on food-seeking behavior extend to drug-seeking. Numerous preclinical studies support this, including findings that semaglutide decreases alcohol intake and cocaine self-administration. We assessed the effects of chronic semaglutide on cocaine-seeking behavior. Adult male and female rats underwent 14 days of cocaine self-administration. Administration was dictated by nose pokes in an “active” port paired with drug infusion and an associated cue light. Rats then underwent 30-days of abstinence to facilitate incubation of drug craving, characterized by time-dependent increases in cue-induced drug seeking. On the fifth day of abstinence, semaglutide or vehicle treatment began. Semaglutide treatment started at an initial dose of 7 µg/kg, which increased incrementally over 10 days to a maintenance dose of 70 µg/kg. This regimen minimizes adverse effects and mirrors human treatment. Rats were placed back into testing chambers after abstinence. Cue-induced reinstatement was assessed as the number of pokes into the active port, resulting in presentation of the drug-associated cue light without infusion. There were no significant effects of semaglutide treatment on cue-induced drug-seeking behavior. Next, drug-induced reinstatement was assessed; rats received escalating doses of cocaine (0, 5, 10, 15 mg/kg, i.p.) prior to placement into testing chambers. Responses in the “active” port had no consequence but served as an index of drug-seeking behavior. At the highest dose, rats treated with semaglutide showed more reinstatement than vehicle-treated rats. Ongoing analyses will determine whether these effects are due to differences in behavioral sensitization to cocaine. These findings suggest that chronic semaglutide treatment during abstinence does not affect cue-induced drug-seeking behavior, but does affect drug-induced drug-seeking behavior.