Behavioral, neurochemical and pharmaco-EEG profiles of the psychedelic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats
- 795 Downloads
Rationale and objectives
Behavioral, neurochemical and pharmaco-EEG profiles of a new synthetic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats were examined.
Materials and methods
Locomotor effects, prepulse inhibition (PPI) of acoustic startle reaction (ASR), dopamine and its metabolite levels in nucleus accumbens (NAc), EEG power spectra and coherence in freely moving rats were analysed. Amphetamine was used as a reference compound.
2C-B had a biphasic effect on locomotion with initial inhibitory followed by excitatory effect; amphetamine induced only hyperlocomotion. Both drugs induced deficits in the PPI; however they had opposite effects on ASR. 2C-B increased dopamine but decreased 3,4-dihydroxyphenylacetic acid (DOPAC) in the NAc. Low doses of 2C-B induced a decrease in EEG power spectra and coherence. On the contrary, high dose of 2C-B 50 mg/kg had a temporally biphasic effect with an initial decrease followed by an increase in EEG power; decrease as well as increase in EEG coherence was observed. Amphetamine mainly induced an increase in EEG power and coherence in theta and alpha bands. Increases in the theta and alpha power and coherence in 2C-B and amphetamine were temporally linked to an increase in locomotor activity and DA levels in NAc.
2C-B is a centrally active compound similar to other hallucinogens, entactogens and stimulants. Increased dopamine and decreased DOPAC in the NAc may reflect its psychotomimetic and addictive potential and monoaminoxidase inhibition. Alterations in brain functional connectivity reflected the behavioral and neurochemical changes produced by the drug; a correlation between EEG changes and locomotor behavior was observed.
Keywords4-Bromo-2,5-dimethoxyphenethylamine (2C-B) Amphetamine Serotonin Dopamine Nucleus accumbens Behavior Microdialysis EEG power spectra EEG coherence Rats
This study was supported by the grants IGA MHCR NS 10374, NS 10375, NT 13897, MEYSCR 1M0517, MHCR MZ0PCP2005, MICR VG20122015075 and VG20122015080. We thank Craig Hampson BSc (Hons) for his helpful comments and language correction.
- Carmo H, de Boer D, Remiao F, Carvalho F, dos Reys LA, de Lourdes BM (2004) Metabolism of the designer drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in mice, after acute administration. JChromatogrB Analyt Technol Biomed Life Sci 811:143–152Google Scholar
- Carmo H, Hengstler JG, de Boer D, Ringel M, Remiao F, Carvalho F, Fernandes E, dos Reys LA, Oesch F, de Lourdes BM (2005) Metabolic pathways of 4-bromo-2,5-dimethoxyphenethylamine (2C-B): analysis of phase I metabolism with hepatocytes of six species including human. Toxicology 206:75–89PubMedCrossRefGoogle Scholar
- EMCDDA (2004) Report on the risk assessment of 2C-I, 2C-T-2 and 2C-T-7 in the framework of the joint action on new synthetic drugs. European monitoring Centre for Drugs and Drug Addiction (EMCDDA)Google Scholar
- Everson CA, Gilliland MA, Kushida CA, Pilcher JJ, Fang VS, Refetoff S, Bergmann BM, Rechtschaffen A (1989b) Sleep deprivation in the rat: IX. Recover Sleep 12:60–67Google Scholar
- Fujakova M, Palenicek T, Tyls F, Kubesova A, Brunovsky M, Krajca V, Horacek J (2011) The effect of phenylethylamine hallucinogens on quantitative electronecephalography and behavior in rats. Behav Pharmacol 22:e38Google Scholar
- Lát J (1973) The analysis of habituation. Acta Neurobiol Exp (Wars) 33:771–789Google Scholar
- Moya PR, Berg KA, Gutierrez-Hernandez MA, Saez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP (2007) Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors. J Pharmacol Exp Ther 321:1054–1061PubMedCrossRefGoogle Scholar
- Palenicek T, Bubenikova V, Votava M, Horacek J (2006) Účinky selektivního antagonisty serotoninového 5-HT2C receptoru SB242084 na lokomoci potkana v animálních modelech psychóz (The effects of selective antagonist of serotonin 5-HT2C receptor SB242084 on rat`s locomotion in animal models of psychosis). Adiktologie 10:16–19Google Scholar
- Palenicek T, Fujakova M, Brunovsky M, Balikova M, Horacek J, Gorman I, Tyls F, Tislerova B, Sos P, Bubenikova-Valesova V, Hoschl C, Krajca V (2011b) Electroencephalographic spectral and coherence analysis of ketamine in rats: correlation with behavioral effects and pharmacokinetics. Neuropsychobiology 63:202–218PubMedCrossRefGoogle Scholar
- Palenicek, T, Fujakova, M, Tyls, F, Kubesova, A, Brunovsky, M, Horacek, J, and Krajca, V (2011d) The impact of behavior on cortical EEG in rats. Neuroimaging through the lifespan: Brain development and brain diseases from adolescence to senescence—Joint meeting of ISNIP/lSBET/ECNS September 7–10, 2011, University of Heidelberg, Germany, Abstrakt Book: 106Google Scholar
- Paxinos G, Watson C (2003) The rat brain in stereotaxic coordinates, 4th edn. Elsevier, Academic Press, New YorkGoogle Scholar
- Shaw JC, O’Connor KP, Ongley OC (1978) EEG coherence as a measure of cerebral functional organization. In: Brazier MB, Petche H (eds) Architectonics of the cerebral cortex. Raven, New York, pp 245–256Google Scholar
- Shulgin A, Shulgin A (1991) PIHKAL: a chemical love story. Transform Press, Berkley, CAGoogle Scholar
- Sumnall H, Wooding O (2009) Mephedrone—an update on current knowledge. Centre for Public Health, Liverpool John Moores UniversityGoogle Scholar
- Syslova K, Rambousek L, Kuzma M, Najmanova V, Bubenikova-Valesova V, Slamberova R, Kacer P (2011) Monitoring of dopamine and its metabolites in brain microdialysates: method combining freeze-drying with liquid chromatography-tandem mass spectrometry. J Chromatogr A 1218:3382–3391Google Scholar
- Tyls F, Palenicek T, Fujakova M, Kubesova A, Brunovsky M, Krajca V, Horacek J (2011) The effect of tryptamine hallucinogens on quantitative EEG and behavior in rats. Behav Pharmacol 22:e39Google Scholar