Microinfusion of bupropion inhibits putative GABAergic neuronal activity of the ventral tegmental area

The most common interpretation for the mechanisms of antidepression is the
increase of the brain monoamine levels such as dopamine (DA). The increase of DA can reduce
depression but it can also decrease the monoamine release because of autoreceptor inhibition.
Although bupropion can decrease the dopamine release, there is evidence about stimulatory
effects of chronic application of bupropion on ventral tegmental area (VTA) neurons. In this
study, the intra-VTA acute microinfusion of bupropion on putative VTA non-Dopaminergic
(VTA-nonDA) neuronal firing rates was evaluated by a single neuron recording technique.
Methods: Animals were divided into 7 groups (sham, and 6 bupropion-microinfused groups
with 1, 10-1, 10-2, 10-3, 10-4, and 10-5 mol, 1 μl/3 min, intra-VTA). A single neuron recording
technique was done according to the stereotaxic coordination. After 10 min baseline recording,
ACSF or bupropion was microinfused. The recording continued to recovery period in the treated
groups. The prestimulus time (PST) and interspike interval (ISI) histograms were calculated for
every single unit. The assessment of the drug effect was carried out by one-way analysis of
variance (ANOVA) and Post-hoc test.
Results: 126 non-DA neurons were separated. Bupropion could inhibit 116 neurons and 11
neurons had no significant response. Maximum inhibition was 79.1% of baseline firing rate with
44.3 min duration. The inhibitory effect of bupropion was dose-dependent.
Discussion: The acute inhibitory effects of bupropion on VTA-nonDA neurons can explain the
fast inhibitory effects of bupropion and other antidepressants on the VTA. These data can explain
some side effects of antidepressants.