Document Type

Restricted

Advisor

Joseph Schroeder

Publication Date

2023

Comments

This honors paper is restricted to users on the Connecticut College campus.

Abstract

Addiction is a public health crisis in our society today. Because drug abuse is so common in our communities, the scientific community is obligated to make sure the treatments available are serving patients the best they can. Current therapies include psychotherapy, inpatient or residential treatment, the use of various behavioral and cognitive intervention strategies, and medical treatments. However, the medical treatments are not tolerated well by all clients and there are not many options to decide between. One objective of pre-clinical drug abuse research is the investigation of different signaling systems in brain reward regions in an attempt to develop new pharmacologic treatment strategies. The chemokine system, which is a signaling system using small proteins called chemokines, helps to regulate the release of dopamine in the mesolimbic system, which is the primary neurotransmitter in reward behavior. Because of this, the chemokine system is a potential target for new addiction medication research. The present study investigated the effects of RAP-103, a multi-chemokine receptor antagonist, on oxycodone-conditioned place preference. Sprague-Dawley rats were exposed to differing drug groups which included 1) oxycodone (1.0 mg/kg), 2) RAP-103 (0.1mg/kg), oxycodone (1.0 mg/kg), 3) RAP-103 (1.0 mg/kg), oxycodone (1.0 mg/kg), and 4) RAP-103 (1.0 mg/kg). Reward behavior of both oxycodone and RAP-103 was assessed using conditioned place preference (CPP). Subjects underwent a 7-day protocol to simulate the development of addiction and reward behaviors. Subjects developed a conditioned place preference to 1.0 mg/kg oxycodone, meaning that oxycodone produces reward behavior. Subjects did not develop a conditioned place preference to 1.0 mg/kg RAP-103, meaning that RAP-103 alone is not rewarding. When RAP-103 and oxycodone were administered together, RAP-103 (0.1 or 1.0 mg/kg) did not significantly affect oxycodone-conditioned place preference. However, trends for both doses of RAP-103 indicate a non-significant enhancement of oxycodone reward behavior. Next steps include continuing to investigate RAP-103 and other multi-chemokine receptor antagonists or agonists. In the future, various trials will be done with differing doses of RAP-103 in addition to the introduction of the drug during the extinction phase of addiction.

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