Ayahuasca treatment reduces 50-kHz ultrasonic vocalizations and modifies mesocorticolimbic monoamine neurochemistry in rats

Rats emit 50-kHz ultrasonic vocalizations (USVs), a widely used measure of drug-induced motivational and affective effects and dopaminergic activity. Although psychedelic drugs are promising for addiction treatment, the effects of ayahuasca (AYA) on 50-kHz ultrasonic vocalizations (USVs) remain unclear. We investigated whether acute AYA treatment attenuates lisdexamfetamine (LDX)-induced USVs, hyperlocomotion and monoaminergic content in adult male Wistar rats. Rats were pretreated with vehicle (VEH) or LDX (10 mg/kg). Forty minutes later, they received VEH or AYA (240 mg/kg) treatment. Behavioral testing was conducted 20 min later in a previous habituated arena during 20 min. Nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were dissected for monoaminergic content analysis by HPLC. AYA treatment reduced the numbers of total 50-kHz, trill and flat USV in VEH and LDX-pretreated groups, with a greater effect size in trill calls. Additionally, AYA attenuated spontaneous locomotion without affecting the LDX-induced hyperlocomotion. The pretreatment with LDX or that with AYA increased the dopamine content in the NAc, but only AYA treatment reduced DOPAC content. All treatments reduced dopamine turnover, as indicated by the DOPAC/dopamine ratio. In the mPFC, AYA treatment increased noradrenaline and decreased serotonin levels without changing their turnover. Both AYA and LDX increased dopamine turnover without altering dopamine content, and AYA did not alter the effects of LDX. Together, these findings suggest that AYA attenuates LDX-induced positive affective responses without reducing hyperlocomotion, accompanied by changes in noradrenaline and serotonin levels in the mPFC and dopamine levels in the NAc.