Burst Firing of the Ventral Tegmental Area Neurons through Bicuculline-Induced GABA-A Receptor Blockade

Ventral Tegmental Area (VTA), as a major source of dopaminergic (DA) neurons, has crucial roles in the vital and pathologic conditions, such as drug dependence and depression. The receptors on the VTA-DA neurons with different density and diversity have modulatory effects on their target tissues, such as the cerebral cortex. The aim of the present study was to study the effect of GABA-A receptor blockade on the VTA-DA neuronal firing pattern.
Male Wistar rats (~200 gr) were randomly allocated in 8 groups with equal substitutive numbers (control, sham, and treatments). The VTA-DA neuronal firing patterns (simple-tonic or burst firing) were acquisitioned under urethane anesthesia and stereotaxic approach. Bicuculline as a GABA-A receptor antagonist were infused microiontophoretically intracerebroventricularly (5, 25, 50, 500, 1000, and 2500 ngr) and peri-injection neuronal firing were captured for burst firing detection.
The simple-tonic spiking of the VTA-DA neurons in the pre-injection period was about 5.78 spikes/sec overall with stable firing. Bicuculline microinjection dose-dependently modulated burst firing pattern. The abovementioned amounts of Bicuculline induced 5.2, 10.4, 23.4, 28.8, 35.9, 36.17 percent of neurons to fire burst with duration of 5.2, 8.7, 24.45, 29.87, 40.56, and 50.34 minutes, respectively. The post injection simple-tonic firing rates were also dose-dependently elevated from 8 to 358 percent of the pre-injection levels.
The results showed that GABA-A receptors on the VTA-DA neurons can have regulatory roles on their firing patterns. The external GABAergic afferents or internal interneurons that mediate GABA modulation on the VTA-DA neurons can interfere in the efferent functions of the VTA-DA neurons.