Honors Theses

Date of Award

2017

Document Type

Undergraduate Thesis

Department

Biomolecular Sciences

First Advisor

Christopher McCurdy

Relational Format

Dissertation/Thesis

Abstract

Sigma receptors have become a popular subject for research the past few decades, but there is still much mystery behind these receptors and how they work. Sigma receptors, like cannabinoid-1 (CB1) receptors, have effects on the human body including appetite regulation, depression, and analgesia. AZ66 is a highly selective sigma receptor ligand that has antagonistic properties. Sigma receptor antagonists have been shown to potentiate the analgesic effects of opiates; however, there are no known literature reports about the interaction between the sigma receptor system and the endocannabinoid system, including CB1 receptors. The purpose of this study is to evaluate AZ66 for potentiation of CB1 related analgesic effects. A tetrad assay was performed for AZ66 using doses 5, 10, and 20 mg/kg (i.p.). The tetrad battery was performed one hour post drug (AZ66) administration. The potentiation study was completed using a 20 mg/kg dose of AZ66 against a 0.3 mg/kg dose of CP 55940. The AZ66 dose was administered one hour before the CP 55940 dose administration, and then the analgesic study was performed 15 minutes post CP 55940 dose administration. The tetrad assay showed that AZ66 exhibited no analgesic effects on its own compared to the control compounds. The potentiation study resulted in significant potentiation of the peripheral analgesic effects of CP 55940 with the addition of AZ66 and insignificant potentiation of central analgesic effects. Future studies will be performed to validate the findings of this study and to further examine the interaction between the sigma receptor system and the cannabinoid system. �

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