Effect of Harmine on Electrically Evoked Dopamine Efflux in the Rat Nucleus Accumbens Core and Shell Brain Slice

Daniel Brierley, Colin Davidson. St George’s University, London, UK

Harmine is the major beta-carboline alkaloid found in the Banisteriopsis caapi vine, a principal component of the traditional Amazonian medicinal infusion Ayahuasca. Anecdotal evidence suggests that consumption of Ayahuasca can reduce incidence of relapse in drug dependent individuals. Here we tested whether harmine had any effect on modulation of evoked dopamine efflux by cocaine, in the rat nucleus accumbens (NAc) brain slice.

NAc brain slices were taken from 8 week old male Wistar rats and maintained in artificial cerebrospinal fluid at 32.5 ± 0.5°C. Dopamine efflux was evoked in either the NAc core or shell using local electrical stimulation (10 x 1 ms, 10 mA pulses at 20 Hz; 450 ms stimulation train) which mimicked midbrain dopamine cell burst firing (1). Dopamine was measured using fast cyclic voltammetry at carbon fibre electrodes (CFE) as previously described (2). We applied a triangular input voltage (-1 to +1.4 V) to the CFE 8 times/s, dopamine oxidised at around 600 mV and we measured the increase in current at this potential.

Results: In the NAc core cocaine (1 µM) increased electrically evoked dopamine efflux and slowed reuptake (reuptake time constant = 195±4% of baseline) as previously shown. Harmine (0.3 µM) had no effect alone or in combination with cocaine either on peak dopamine efflux or dopamine reuptake. In the NAc shell cocaine again increased peak dopamine efflux and slowed reuptake (time constant = 189±19% of baseline). Harmine increased peak dopamine efflux (by 50%), and also increased peak dopamine efflux by a further 80% in combination with cocaine. The effect of harmine on dopamine efflux was attenuated by 60 min pre-treatment with the 5-HT2A/C receptor antagonist ketanserin (1 µM).

Table 1. Effect of harmine on peak dopamine efflux in the NAc shell. Values are means ± SEM expressed as a percentage of baseline values. N = 5-7 for each group. *P<0.05 vs control (two-way ANOVA).

Conclusions: Harmine can increase peak dopamine efflux in the NAc shell, but not the NAc core. This effect is attenuated by pre-treatment with ketanserin showing that harmine acts via activation of 5-HT22A/C receptors.

 (1) Hyland et al (2002) Neuroscience 114, 475-492.

 (2) Davidson et al (2011) J Neuroscience Methods (in press)