Thesis Defense Announcement

College of Arts and Sciences announces the Final Thesis Defense of

Kevin Honeywell

for the Degree of Master of Science

July 15, 2019 at 1:00 PM Psychology Building, Room 208

Advisor: Helen Sable

Examining the Chronic Effects of Indirect and Direct Cannabinoid Receptor Agonists on Dopamine Transmission in the Nucleus Accumbens of Mice

ABSTRACT: A major problem with current anxiolytic medications is abuse liability; thus, new pharmaceutical targets are being explored. Cannabinergic and vanilloidergic signaling are of interest in the modulation of anxiety through cannabinoid type 1 receptor (CB1R) activation and transient vanilloid type 1 channel (TRPV1) inhibition. Arachidonoyl serotonin (AA-5-HT), a dual fatty acid amide hydrolase (FAAH) and TRPV1 inhibitor, is a drug of interest in modulating these two systems and has been shown to modestly reduce anxiety-related behaviors and dopamine release in the nucleus accumbens (Freels, Lester, & Cook, 2019; Maione et al., 2007; Micale et al., 2009). The current study explored the addictive potential of chronic AA-5-HT or arachidonyl-2-chloro-ethylamide (ACEA), a direct CB1R agonist, administration through locomotor activity in the open field (OF), in vivo fixed potential amperometry (FPA) for ventral tegmental area (VTA) stimulated dopamine efflux in the nucleus accumbens (NAc), conditioned place preference (CPP) for these two drugs, and saccharin two-bottle choice test. AA-5-HT did not significantly alter locomotor activity in the OF, dopamine efflux in the NAc during FPA, place preference during CPP, and saccharin preference. ACEA significantly reduced baseline dopamine release, altered drug challenge evoked dopamine release in a pretreatment- and time-dependent manner, and, through pretreatment, enhanced cocaine drug challenge induced increases in dopamine half-life, but did not alter locomotor activity in the OF, induce CPP or a shift in saccharin preference. These results suggest these drugs present little addictive potential.