Brief Article
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World J Biol Chem. Nov 26, 2013; 4(4): 141-147
Published online Nov 26, 2013. doi: 10.4331/wjbc.v4.i4.141
Changes in aminoacidergic and monoaminergic neurotransmission in the hippocampus and amygdala of rats after ayahuasca ingestion
Eduardo Ferreira de Castro-Neto, Rafael Henrique da Cunha, Dartiu Xavier da Silveira, Mauricio Yonamine, Telma Luciana Furtado Gouveia, Esper Abrão Cavalheiro, Débora Amado, Maria da Graça Naffah-Mazzacoratti
Eduardo Ferreira de Castro-Neto, Rafael Henrique da Cunha, Telma Luciana Furtado Gouveia, Esper Abrão Cavalheiro, Débora Amado, Departamento Neurologia/Neurocirurgia, Universidade Federal de São Paulo, São Paulo, SP 04023900, Brazil
Dartiu Xavier da Silveira, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, SP 04023900, Brazil
Mauricio Yonamine, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP 05508000, Brazil
Maria da Graça Naffah-Mazzacoratti, Departamento de Bioquímica, Universidade Federal de São Paulo, SP 04023900, Brazil
Author contributions: Silveira DX and Naffah-Mazzacoratti MG were responsible for the study concept and design; Castro-Neto EF and Cunha RH contributed to the acquisition of animal data; Castro-Neto EF performed the HPLC analysis; Castro-Neto EF and Naffah-Mazzacoratti MG assisted with data analysis and interpretation of findings; Yonamine M described the drug components; Silveira DX provided the drug and performed analytical tests; Gouveia TLF, Cavalheiro EA, Amado D and Naffah-Mazzacoratti MG provided critical revision of the manuscript for important intellectual content; all the authors critically reviewed the content and approved the final version for publication.
Supported by Fundação de Amparo a Pesquisa do Estado de São Paulo; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Conselho Nacional de Desenvolvimento Científico e Tecnológico; Instituto Nacional de Neurociência Translacional
Correspondence to: Maria da Graça Naffah Mazzacoratti, PhD, Associate Professor, Departamento de Bioquímica da Universidade Federal de São Paulo, Rua Pedro de Toledo 669, Edificio de Pesquisa II, 2.o andar, São Paulo, SP 04039032, Brazil. naffahmazz.nexp@epm.br
Telephone: +55-11-55764848 Fax: +55-11-55764848
Received: May 12, 2013
Revised: September 29, 2013
Accepted: October 17, 2013
Published online: November 26, 2013
Abstract

AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats.

METHODS: The level of monoamines, their main metabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography (HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion (gavage). Animals were killed 40 min after drug ingestion and the structures stored at -80 °C until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P < 0.05 was accepted as significant.

RESULTS: The results showed decreased concentrations of glycine (GLY) (0.13 ± 0.03 vs 0.29 ± 0.07, P < 0.001) and γ-aminobutyric acid (GABA) (1.07 ± 0.14 vs 1.73 ± 0.25, P < 0.001) in the amygdala of rats that received 500 of ayahuasca. Animals that ingested 800 mg/kg of ayahuasca also showed a reduction of GLY level (0.11 ± 0.01 vs 0.29 ± 0.07, P < 0.001) and GABA (0.98 ± 0.06 vs 1.73 ± 0.25, P < 0.001). In the hippocampus, increased GABA levels were found in rats that received all ayahuasca doses: 250 mg/kg (1.29 ± 0.19 vs 0.84 ± 0.21, P < 0.05); 500 mg/kg (2.23 ± 038 vs 084 ± 0.21, P < 0.05) and 800 mg/kg (1.98 ± 0.92 vs 0.84 ± 0.21, P < 0.05). In addition, an increased utilization rate of all monoamines was found in the amygdala after ayahuasca administration in doses: 250 mg/kg (noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P < 0.01; dopamine: 0.39 ± 0.012 vs 2.39 ± 0.84, P < 0.001; serotonin: 1.02 ± 0.22 vs 4.04 ± 0.91, P < 0.001), 500 mg/kg (noradrenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.33 ± 0.19 vs 2.39 ± 0.84, P < 0.001; serotonin: 0.59 ± 0.08 vs 4.04 ± 0.91, P < 0.001) and 800 mg/kg (noradrenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs 2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001).

CONCLUSION: Our data suggest increased release of inhibitory amino acids by the hippocampus and an increased utilization rate of monoamines by the amygdala after different doses of ayahuasca ingestion.

Keywords: Ayahuasca, Amino Acids, Monoamines, Hippocampus, Amygdala

Core tip: Several studies have indicated that the main component of ayahuasca, N,N-dimethyltryptamine (DMT), is structurally similar to serotonin (5-hydroxytryptamine or 5-HT) and also has similarities with lysergic acid and mescaline, normally employed in drug addiction. This infusion contained DMT as a principal ingredient in a psychoactive beverage, used by more than 70 different indigenous groups spread throughout Brazil, Colombia, Peru, Venezuela and Ecuador. In human beings, it is also present in the brain as an endogenous substance and is found in blood, urine and cerebrospinal fluid. After oral administration of ayahuasca at different doses to naïve rats, we found that ayahuasca ingestion could modify neurotransmitter release in limbic brain structures.