Figure 6. A predicted non-hallucinogenic compound with antidepressant potential.
A. Representative images demonstrating that AAZ-A-154 promotes dendritic branching. Scale bar: 20 μm B. Maximal number of crossings (Nmax) from Sholl plots (n = 51–60 neurons). ****p<0.0001, ***p<0.001, one-way ANOVA with Dunnett’s test. C. The effects of AAZ (100 nM) on dendritic growth can be blocked by the 5-HT2R antagonist ketanserin (KETSN, 1 μM, n= 39–58 neurons). ****p<0.0001, one-way ANOVA with Dunnett’s test. D. Schematic depicting the forced swim test design. AAZ-A-154 (20 mg/kg) produces fast (30 min) and long-lasting (1 week) antidepressant-like effects in the FST comparable to ketamine (KET) (n= 12). ****p<0.0001, ***p<0.001, and *p<0.05, one-way ANOVA with Dunnett’s test. E. Sucrose preference test reveals that AAZ (15 mg/kg) reduces anhedonia in VMAT2-HET mice for at least 12 days. Water-water pairing = W-W, water-sucrose (1%) pairing = W-S. When given the choice between water and a 1% sucrose solution (W-S), only WT mice displayed a sucrose preference. Total fluid consumption was not different between genotypes at any time point. N = 11 mice/genotype; data are represented as means and SEMs, **p<0.01 and *p<0.05, WT vs. VMAT2-HET, repeated measures ANOVA with Bonferroni corrected pair-wise comparisons.