Harmine augments electrically evoked dopamine efflux in the nucleus accumbens shell
Daniel I. Brierley, Colin Davidson
Journal of Psychopharmacology October 17, 2012 DOI: 10.1177/0269881112463125 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rat brain slices |
| Interventions | Harmine Cocaine Ketanserin Moclobemide |
| Dose | Harmine 300 nM; Moclobemide 10 µM |
| Measures | electrically evoked DA efflux measured by fast cyclic voltammetry |
| Topics | Ayahuasca |
| Keywords | Harmine Nucleus accumbens Pharmacology Agonist Dopaminergic Efflux |
| Citations | 42 |
| Key findings | Harmine augments dopamine efflux in the nucleus accumbens shell via a 5-HT2A receptor-dependent mechanism independent of MAO inhibition. |
Abstract
Harmine is a β-carboline alkaloid and major component of ayahuasca, a traditional South American psychoactive tea with anecdotal efficacy for treatment of cocaine dependence. Harmine is an inhibitor of monoamine oxidase A (MAO-A) and interacts in vitro with several pharmacological targets which modulate dopamine (DA) neurotransmission. In vivo studies have demonstrated dopaminergic effects of harmine, attributed to monoamine oxidase inhibitor (MAOI) activity, however none have directly demonstrated a pharmacological mechanism. This study investigated the acute effects, and pharmacological mechanism(s), of harmine on electrically evoked DA efflux parameters in the nucleus accumbens both in the absence and presence of cocaine. Fast cyclic voltammetry in rat brain slices was used to measure electrically evoked DA efflux in accumbens core and shell. Harmine (300 nM) significantly augmented DA efflux (148±8% of baseline) in the accumbens shell. Cocaine augmented efflux in shell additive to harmine (260±35%). Harmine had no effect on efflux in the accumbens core or on reuptake in either sub-region. The effect of harmine in the shell was attenuated by the 5-HT 2A/2C antagonist ketanserin. The MAOI moclobemide (10 µM) had no effect on DA efflux. These data suggest that harmine augments DA efflux via a novel, shell-specific, presynaptic 5-HT 2A receptor-dependent mechanism, independent of MAOI activity. A DA-releasing ‘agonist therapy’ mechanism may thus contribute to the putative therapeutic efficacy of ayahuasca for cocaine dependence.
Comparable studies
Other preclinical and animal studies on ayahuasca, most cited first.
Citations in the library
Cited by 29
- Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Therapeutic Advances in Psychopharmacology March 18, 2016
- Ayahuasca: Psychological and Physiologic Effects, Pharmacology and Potential Uses in Addiction and Mental Illness Current Neuropharmacology March 2, 2018
- The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging Journal of Psychopharmacology June 11, 2016
- Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat Behavioural Processes June 6, 2015
- Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans Journal of Psychoactive Drugs May 26, 2016
and 24 more in the library
Cites 8
- Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca Journal of Ethnopharmacology April 1, 1984
- Human Psychopharmacology of Hoasca, A Plant Hallucinogen Used in Ritual Context in Brazil The Journal of Nervous and Mental Disease February 1, 1996
- Assessment of addiction severity among ritual users of ayahuasca Drug and Alcohol Dependence June 17, 2010
- Developments in harmine pharmacology — Implications for ayahuasca use and drug-dependence treatment Progress in Neuro-Psychopharmacology and Biological Psychiatry June 10, 2012
- beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association March 1, 2010
and 3 more in the library