Influences of SALVINORIN A and SEX DIFFERENCES on DEPRESSIVE- AND ANXIETY-LIKE behaviors in a CHRONIC MILD STRESS paradigm
Master of Arts
Date of Defense
Dr. George T. Taylor
Dr. Suzanne Welcome
Dr. Jodi Woodruff
Kappa opioid receptors are colocalized with dopamine receptors and are frequently associated with depression, anxiety, stress, and drug use and abuse. KOR antagonism has widely been considered anti-depressive and anxiolytic in animal models while agonism is pro-depressive and anxiogenic. However, recent findings suggest that SalvA, a natural kappa agonist derived from a plant in the mint family, can reduce depressive- and anxiety-like behavior in rats. The current study investigated the effects of chronic mild stress on behavior, attenuation by SalvA, and sex differences. 52 Long-Evans rats, 26 males and 26 females, were exposed to six weeks of CMS. Animals received daily injections of either SalvA or vehicle for the last three weeks of the experiment. Behavioral tests were administered at baseline, three weeks, and six weeks. We predicted that CMS would induce the depressive-like behaviors anhedonia and learned helplessness, as measured by reduced sucrose preference and increased immobility in the forced swim test, respectively. We also predicted that CMS would induce anxiety-like behavior by reducing exploratory behavior and increasing immobility in the open field test. It was predicted that SalvA exposure would attenuate the effects of CMS. Further, we predicted that female rats would be more sensitive to the effects of stress but also show greater response to SalvA. Results showed that CMS did not reliably induce depressive- or anxiety-like behaviors. Because there were no reliable behavioral changes due to stress, the potential antidepressant or anxiolytic effects of SalvA were not apparent. In the male drug group, SalvA appeared to increase anxious behavior in the open field test and depressive-like behavior in the forced swim test, aligning with previous findings that KOR agonists can be anxiogenic and pro-depressive. Additionally, results showed that behavior in the forced swim and open field tests were sex dependent, with males showing more depression- and anxiety-like behaviors than females. More research is necessary to better understand the effects of CMS and SalvA on behavior. Closer examination of the behavioral paradigms measuring depression and anxiety in animals is needed and future research should carefully consider sex differences when employing these behavioral paradigms.
Mitchell, Sarah, "Influences of SALVINORIN A and SEX DIFFERENCES on DEPRESSIVE- AND ANXIETY-LIKE behaviors in a CHRONIC MILD STRESS paradigm" (2020). Theses. 394.
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