1. Investigating a Novel Neutral Antagonist, 6Beta-Naltrexol, in Alleviating Cocaine Withdrawal Symptoms Timothy DeYoung, Michelle Mueller, and Dr. Boyette-Davis Department of Biological Sciences, York College of Pennsylvania Introduction Addiction is a debilitating condition which can lead to compulsive behavior, continued abuse of drugs, and persistent changes in the brain’s structure and function. Relapse rates for individuals with a history of drug abuse can be as high as 90%. Cocaine, a drug known for its addictive properties, is also known to have high relapse rates. A common treatment for cocaine addiction is Naltrexone (NTX), which blocks mu-opioid receptors. However NTX has issues in regards to initially increasing withdrawal symptoms (Guiliano et al. 2013). 6beta-Naltrexol, a neutral antagonist, has been used in studies relating to decreased alcohol consumption in addicted rats (Stromberg et al. 2002), and has also been found to decrease withdrawal symptoms from opiates in a recent study (Navani et al. 2011). Cohort 1 (n=9) Sep 11-Oct 2 Naltrexone Day 15, 22 6beta-Naltrexol Day 15,22 Vehicle (Saline) Day 15,22 PreSwim FST Day 14 Cocaine Dependence Days 1-14 Baseline Testing Day 1 Cohort 2 (n=9) Sep 28-Oct 19 DV Testing Day 15, 22 Cohort 3 (n=9) Oct 12-Nov 2 Procedure Objectives 1.Determine if 6beta-Naltrexol can help reduce withdraw symptoms in addicted rats. 2.Assess the effectiveness of 6beta-Naltrexol in alleviating withdraw symptoms in addicted rats in comparison to the well known effects of Naltrexone. 3.Observe classic withdrawal symptoms in Sprague Dawley rats utilizing the elevated plus maze (EPM) for anxiety and the forced swim test (FST) for depression. Conclusions 1.6beta-Naltrexol was successful in alleviating the symptoms of cocaine withdrawal showing a statistical significance after adjusting for the high and low responders when compared to the Vehicle group in the FST. 2.Naltrexone was consistent with the literature and unfortunately worked better than 6beta-Naltrexol in reducing both anxiety and depression within the EPM and FST. 3.6beta-Naltrexol could possibly be a suitable alternative for Naltrexone, as it is shown here to decrease depression in addicted rats. 4.With this treatment it may allow an individual to overcome the initial increase in withdraw symptoms due to the inverse agonist actions of Naltrexone. 5.Further research is being conducted on whether or not the Mu-opioid receptors were affected by this treatment, changes will be observed by using immunohistochemistry. Literature Cited Giuliano, C. Robbins, T.W., Wille, D.R. 2013. Attenuation of cocaine and heroin seeking by u-opioid receptor antagonism. Psychopharmacology 227: 137-147 Navani, D.M., Sirohi, S., Madia, P. A., Yoburn, B. C., 2011. The role of opioid antagonist efficacy and constitutive opioid receptor activity in the opioid withdrawal syndrome in mice. Journal of Pharmacology Biochemistry and Behavior. 99(4):671-675 Stromberg, M.R., Rukstalis, M.R., Mackler, S.A., Volpicelli, J.R., O’Brien, C.P. 2022. A comparison of the effects of 6- β Naltrexol and naltrexone on the consumption of ethanol or sucrose using a limited-access procedure in rats. Journal of Pharmacology Biochemistry and Behavior. 72: 483-490 Future Studies Evaluate and determine if varying the dosage has any effect on withdrawal symptoms. Methods/Materials Male SD rats, aged 60 days Housing- 3 per cage Free access to food and water 12:12 light dark cycle Cocaine: 15mg/kg 6beta-Naltrexol: 15mg/kg Naltrexone: 1mg/kg Vehicle: Saline Acknowledgements I would like to thank both the Biology and Psychology department of York College of Pennsylvania for the use of their laboratories and equipment. I would also like to thank Michelle Mueller for the assistance in conducting the experiment. Finally I would like to extend my gratitude to Dr. Boyette-Davis and Dr. Thompson for their guidance and support throughout my research. http://www.abcam.com/mu-opioid-receptor-antibody-ab10275.html http://www.janvier-labs.com/rodent-research-models-services/research- models/per-species/outbred-rats/product/sprague-dawley.html * Results Elevated Plus Maze Forced Swim Test * * * *