Ayahuasca treatment reduces 50-kHz ultrasonic vocalizations and modifies mesocorticolimbic monoamine neurochemistry in rats.
Camila Pasquini De Souza, Vinicius Theiss De Rosso, Daiane Momo Daneluz, Jeferson Machado Batista Sohn, José Guilherme Silva De Almeida, Gisele De Oliveira Guaita, Gabriella Honorio Vieira, Gabriela O Silveira, Mauricio Yonamine, Rainer K.W. Schwarting, Roberto Andreatini, Cristina Aparecida Jark Stern
Pharmacology, Biochemistry, and Behavior September 30, 2026 DOI: 10.1016/j.pbb.2026.174274 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Adult male Wistar rats |
| Interventions | Ayahuasca Lisdexamfetamine |
| Dose | Ayahuasca 240 mg/kg; lisdexamfetamine 10 mg/kg |
| Measures | 50-kHz ultrasonic vocalizations (USVs), locomotor activity, HPLC monoaminergic content analysis |
| Topics | Addiction Serotonin Ayahuasca |
| Keywords | Amphetamine Dopamine Mao-a Noradrenaline Nucleus accumbens Prefrontal cortex |
| Key findings | Ayahuasca reduced total, trill, and flat 50-kHz ultrasonic vocalizations in both vehicle- and lisdexamfetamine-pretreated rats, with the strongest effect on trill calls, and reduced spontaneous locomotion without affecting lisdexamfetamine-induced hyperlocomotion. It also altered nucleus accumbens dopamine metabolism and medial prefrontal cortex noradrenaline and serotonin levels. The authors suggest ayahuasca attenuates lisdexamfetamine-induced positive affective responses without reducing hyperlocomotion. |
Abstract
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.
In the evidence
This study is part of the evidence base for 3 syntheses in the library. Here is how each one recorded it.
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Ayahuasca reduced 50-kHz ultrasonic vocalizations (including trill and flat calls) in vehicle- and lisdexamfetamine-pretreated rats and altered mesocorticolimbic monoamine metabolism, suggesting attenuation of drug-induced positive affective responses.
Synthesized
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Ayahuasca reduced 50-kHz ultrasonic vocalizations and spontaneous locomotion and altered mesocorticolimbic monoamine levels, but did not reduce lisdexamfetamine-induced hyperlocomotion.
Synthesized
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Ayahuasca reduced 50-kHz ultrasonic vocalizations and spontaneous locomotion and altered mesocorticolimbic monoamine levels, including decreased medial prefrontal serotonin.
Synthesized
Comparable studies
Other preclinical and animal studies on ayahuasca for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice Mice | 2015 | Experimental study | |
| Effects of the hallucinogenic beverage ayahuasca on voluntary ethanol intake by rats and on cFos expression in brain areas relevant to drug addiction Wistar rats | 2019 | Animal experiment | |
| Ayahuasca blocks ethanol preference in an animal model of dependence and shows no acute toxicity Mice | 2021 | Preclinical study | |
| Phytochemical and Neuropharmacological Evaluation of Banisteriopsis caapi, Paullinia cupana, and Turnera diffusa for Potential Anti-Addiction Activity | 2026 | Computational and in vitro study | |
| Ayahuasca prevents the reinstatement of cocaine-induced rewarding effects in C57Bl/6 mice. C57Bl/6 mice | 2025 | Experimental study |
Citations in the library
Cites 23
- Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report Brazilian Journal of Psychiatry March 1, 2015
- Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Current Drug Abuse Reviews June 1, 2013
- Assessment of addiction severity among ritual users of ayahuasca Drug and Alcohol Dependence June 17, 2010
- Ayahuasca: Pharmacology, neuroscience and therapeutic potential Brain Research Bulletin March 11, 2016
- Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Brain Research September 19, 1994
and 18 more in the library