An Evaluation of the Relationship between Sigma-1 and Sigma-2 Receptors and the Endocannabinoid System

Miller, Jenn (2016) An Evaluation of the Relationship between Sigma-1 and Sigma-2 Receptors and the Endocannabinoid System. Undergraduate thesis, under the direction of Christopher McCurdy from BioMolecular Sciences, School of Pharmacy, University of Mississippi.

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Abstract

Within the past two decades, sigma receptors have become a popular area for research. Although much has been learned about their structure, subtypes, and functions; there is still much to be learned. Consisting of two receptor subtypes (sigma-1 and sigma-2), it has been discovered that sigma receptor ligands potentiate the analgesic effects of both opiates and cannabinoids, though the exact mechanism and sigma subtype on which this occurs is still unknown. The purpose of this study is to determine if potentiation of opiates and cannabinoids occurs through sigma-1 or sigma-2 receptor signaling. Tetrad assays were performed for: 1. Morphine, an opiate, at multiple doses (i.p.), 2. CP 55,940, a cannabinoid, at multiple doses (i.p.), 3. CM304, a sigma-1 antagonist, at multiple doses (i.p.), and 4. CM398, a sigma-2 antagonist, at multiple doses (i.p.). The potentiation studies were then completed by using both 20 and 45 mg/kg doses of CM304 and CM398 against either a 1 mg/kg dose of CP 55,950 or a 2 mg/kg dose of morphine. The CM dose was administered 15 minutes before the CP or the morphine dose, and the analgesic study was performed 15 minutes post CP or morphine administration. This study revealed that CM304, the sigma-1 antagonist, potentiated the effects of CP 55,940 and morphine for the hotplate assay while it attenuated the effects on the tail-flick assay. Additionally, CM398, the sigma-2 antagonist, failed to potentiate both CP 55,940 and morphine for both the hotplate and the tail-flick assay. Results also showed that AZ66, the general sigma receptor antagonist, potentiated the effects of CP 55,940 for both the hotplate and the tail-flick assays. In conclusion, administering a sigma-1 antagonist, instead of a sigma-2 antagonist, in conjunction with either an opiate or a cannabinoid will potentiate the effects of the challenge drug. This can serve as an important basis for the future of pain research.

Item Type: Thesis (Undergraduate)
Creators: Miller, Jenn
Student's Degree Program(s): B.A. in General Studies and B.S. in Pharmaceutical Sciences
Thesis Advisor: Christopher McCurdy
Thesis Advisor's Department: BioMolecular Sciences, School of Pharmacy
Institution: University of Mississippi
Subjects: R Medicine > RM Therapeutics. Pharmacology
Depositing User: Jenn Miller
Date Deposited: 26 Apr 2016 20:13
Last Modified: 26 Apr 2016 20:14
URI: http://thesis.honors.olemiss.edu/id/eprint/497

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