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Harmine augments electrically evoked dopamine efflux in the nucleus accumbens shell

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pitubo

dysfunctional word machine
Senior Member
http://jop.sagepub.com/content/early/2012/10/12/0269881112463125.abstract

Harmine augments electrically evoked dopamine efflux in the nucleus accumbens shell
Daniel I Brierley, Colin Davidson
J Psychopharmacol January 2013 vol. 27 no. 1 98-108
doi: 10.1177/0269881112463125

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-HT2A/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-HT2A 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.
 

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These data suggest that harmine augments DA efflux via a novel, shell-specific, presynaptic 5-HT2A 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.

This makes sense, as those dependant on cocaine are going to have dopamine issues, I've always wondered pharmacologically how harmine would be effective it in treating cocaine and amphetamine dependence.

Cocaine is a dopamine releasing agent as well as a dopamine reuptake inhibitor, the chronic dopamine release depletes endogenous stores of the compound. Inhibition of the reuptake channel leaves free floating dopamine trapped in the synapse for an extended period of time, damaging the neuron...

So it's no surprise that "dopamine agonist therapy" facilitated via harmine would be helpful...


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Harmine treating Parkinson's mentioned in TIHKAL:

It was Louis Lewin, of Phantastica fame, who first suggested that banisterine might be useful in the treatment of disease of the nervous system. And it was Kurt Beringer, of der Meskalinrausch fame, who ran the first clinical study using banisterine on 15 patients with postencephalitic parkinsonism, in 1928. Other studies reinforced the virtues of this drug. Initially, doses of 20 or 40 mg were administered intramuscularly, and within 15 minutes the patients had less motor rigidity and were able to move more freely. Even when used orally, at 10 mg thrice daily, the responses were remarkable. In some cases the tremor was diminished, and in others it was exaggerated, but in general the mental status of the patients was brightened, without producing "psychic" effects. Banisterine became the wonder drug of the year, the feature stuff of the Sunday Supplements. -shulgin


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-eg
 
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