Fig. 5: Regional AAL-mediated ketamine uncaging selectively activates site-differential behavioural efficacy.
a, Rats undergoing awake restraint-induced acute stress were administered intravenously either SonoKet (0.75 mg kg−1), dose-matched KetHCl or saline for 5 min, with fully transcranial sonication applied to either the mPFC or RsC at t = 2.5-5 min. Rats were then released and placed in an open-field test box and filmed from above in a well-lit room (https://BioRender.com/59296sm). b, Tracks for all rats overlaid for each group, by treatment and sonicated region. All treatment groups received ultrasound at either the mPFC (top) or RsC (bottom). c,d, Total distance travelled within each treatment group averaged across subjects (one recording per animal) in 1 min time bins plotted across time (c) and averaged across the entire recording (d). Data presented as box plots. One-way, two-sided, ANOVA followed by Tukey’s post hoc HSD for multiple comparisons showed no significant differences; n = 6 rats per group. e,f, Average speed over the first 5 min of recording for each treatment group averaged across subjects plotted across time (e) and averaged across the first 5 min of recording (f). Data presented as box plots. One-way, two-sided, ANOVA followed by Tukey’s post hoc HSD for multiple comparisons showed no significant differences; n = 6 rats per group. g,h, Percentage of time spent in the centre versus edge of the field for each treatment group averaged across subjects (one recording per animal) in 1 min time bins plotted across time (g) and averaged across the entire recording (h). mPFC: saline versus SonoKet (P = 0.037, Hedges g = 1.24); KetHCl versus SonoKet (P = 0.028, Hedges g = 1.35). RsC: no significant differences. Data presented as line plots are presented as mean ± s.e. Data presented as box plots show minima, maxima, interquartile range (box bounds) and median (white line). One-way, two-sided, ANOVA followed by Tukey’s post hoc HSD for multiple comparisons; *P < 0.05; n = 6 rats per group.
