Andrea Cippitelli, PhD
Florida Atlantic University
Co-Authors: Michael Lauber1, Meira Gildin1, Thamires Righi1, Fernando Rodriguez de Fonseca2,3
1Florida Atlantic University, 2Instituto de Investigación Biomédica de Málaga, 3Galea Therapeutics
Background: Alcohol use disorder (AUD) is frequently co-morbid in patients suffering from post-traumatic stress disorder (PTSD). Few therapeutic options are available for the individual disorders, and there are currently no drugs specifically shown to treat AUD in patients with comorbid PTSD. This is in part because it has been challenging to produce reliable animal models that allow evaluation of pharmacological interventions for the comorbidity. Oleoylethanolamide (OEA), an endocannabinoid-like lipid signaling molecule, which functions as a satiety factor, has been reported to decrease alcohol self-administration in rats and preclinical manifestations associated with stress exposure such as stress-induced anxiety-like behavior and prepulse inhibition.
Methods: Here, female and male Sprague-Dawley rats were initially trained to respond for alcohol in operant chambers. Their response was extinguished and then re-established by cues previously associated with alcohol availability. All rats were then subjected to Single Prolonged Stress to induce PTSD-like symptoms. Afterward, anxiety-like behavior of individual rats was assessed and a second cue-induced reinstatement was conducted.
Objective: To test the model of alcohol relapse combined with exposure to traumatic stress we used OEA (4 mg/kg, ip) and N-oleoylsulfamide (1 and 4 mg/kg, ip), a compound licensed by Galea Therapeutics. Like OEA, N-oleoylsulfamide binds at peroxisome proliferator-activated receptors-a (PPAR-a).
Results: Results support the efficacy of PPAR-a agonists to reduce the escalated as well as non-escalated alcohol-seeking behavior in male rats. Research in the females is ongoing.
Conclusions: OEA and N-oleoylsulfamide could represent potentially novel pharmacotherapies for AUD-PTSD comorbidity.
Support: The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Alcohol and Substance Use Research Program under Award No. W81XWH-18-2-0044. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. In conducting research using animals, the investigator(s) adhered to the laws of the United States and the regulations of the Department of Agriculture.