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Recent clinical trials have demonstrated favorable therapeutic outcomes with psychedelics for anxiety and treatment-resistant depression. Whereas the mechanisms underlying their putative therapeutic effects are not well understood, nonhuman models can serve to investigate these mechanisms. The current study implemented two rodent models predictive of traditional anxiolytic drug effects, a light/dark test and an elevated plus maze (EPM) to investigate the acute and sub-chronic effects of LSD, respectively. Forty-eight, adult male Sprague-Dawley rats were randomly assigned to LSD (0.02, 0.04, 0.08 mg/kg) treatments and assessed in the light/dark test. These treatments continued every 48 hours for a total of six injections, after which the same rats were assessed in the EPM either 48 (n=24) or 72 hours (n=24) after the last dose. A dose-dependent and statistically significant decrease in entries into and time spent in the brightly lit compartment was observed in the light/dark test, with no statistically significant difference in overall activity among treatment groups. In the EPM, LSD-treated rats assessed 48 hours after the last injection made more entries into and spent significantly more time in the closed arms compared to saline-treated rats. In contrast, rats tested 72 hours after the last injection showed no statistically significant difference in open versus closed arm entries or time spent in either arm type. These results indicate acute and brief intermittent treatment with LSD produces anxiogenic effects, though these effects did not persist after a 72 hour drug washout. These findings are consistent with previous reports of mild anxiogenic effects following sub-chronic, intermittent low-dose treatment with psilocin or ketamine in the EPM test. In consideration of positive therapeutic outcomes with hallucinogens in psychedelic-assisted psychotherapy, alternative preclinical models may be warranted to discern the mechanisms underlying their putative therapeutic effects.
Conway, Catherine, "Anxiogenic Effects of Lysergic Acid Diethylamide in Adult Sprague-Dawley Rats" (2020). Honors Theses. 3335.
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