Neuroimaging & Brain Measures2C-X

Behavioral, neurochemical and pharmaco-EEG profiles of the psychedelic drug 4-bromo-2, 5-dimethoxyphenethylamine (2C-B) in rats

This rat study investigates the behavioral, neurochemical, and EEG profiles 2C-B. 2C-B demonstrates biphasic effects on locomotion, initially inhibitory and then excitatory, contrasting with amphetamine which induces solely hyperlocomotion. Both compounds disrupt prepulse inhibition (PPI) of the startle reaction, albeit with different effects on acoustic startle response (ASR). In the nucleus accumbens (NAc), 2C-B increases dopamine levels but decreases 3,4-dihydroxyphenylacetic acid (DOPAC), suggesting potential psychotomimetic and addictive properties. EEG analyses reveal that low doses of 2C-B reduce power spectra and coherence, whereas high doses show biphasic effects on EEG power and coherence.

Authors

  • Tomáš Páleníček
  • František Tylš
  • Martin Brunovský

Published

Psychopharmacology
individual Study

Abstract

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.

Results: 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.

Conclusions: 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.

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Research Summary of 'Behavioral, neurochemical and pharmaco-EEG profiles of the psychedelic drug 4-bromo-2, 5-dimethoxyphenethylamine (2C-B) in rats'

Blossom's Take

As one of the few studies on 2C-B conducted (or at least in our database), this study provides valuable insights into how this compound - loved by Sasha Shulgin - works in the brain, influencing a variety of neurotransmitters.

Introduction

Páleníček and colleagues describe 4-bromo-2,5-dimethoxyphenethylamine (2C-B), a recreational phenylethylamine with reported psychedelic and entactogenic effects, as one of a family of “2Cs” whose human use outstrips detailed preclinical characterisation. Earlier literature provided limited behavioural data (one older human study and a single avian study) and little information on monoamine neurotransmission; binding data suggested partial agonism at serotonin 5-HT2A/2C and 5-HT1A/B receptors but left gaps about dopaminergic effects and whole-brain functional consequences. The authors positioned 2C-B between classic psychedelics and entactogens such as MDMA, and noted the need to assess behavioral, neurochemical and electrophysiological actions in a rodent model to better understand its pharmacology and potential risks. The study set out to provide an integrated characterisation in rats, combining open-field locomotion and sensorimotor gating (prepulse inhibition of acoustic startle, PPI), microdialysis of dopamine and metabolites in nucleus accumbens (NAc), and quantitative EEG (QEEG) from 12 cortical electrodes. Amphetamine was included as a comparator stimulant to help dissociate entactogenic/serotonergic from stimulant/dopaminergic effects. The investigators emphasised time-dependent assessments to capture both onset and peak-brain-concentration phases after subcutaneous dosing, and they aimed to relate behavioural changes to neurochemical and EEG markers of brain functional connectivity.

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References (2)

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