GABAB receptor-mediated mechanisms in the RVLM studied by microinjections of two GABAB receptor antagonists

GIAN LUIGI AVANZINO, PIER0 RUGGERI, DONATELLA BLANCHI, CARLA E. COGO, ROSA ERMIRIO, AND LYNNE C. WEAVER
Istituto di Fisiologia Umana, Universith degli Studi, Viale Benedetto XV 3, I-l 6132 Genoa, Italy; and The John P. Robarts Research Institute, London, Ontario N6A 5K8, Canada
Journal of American Physiology Society (1994)

The current study is one of the first to investigate the role of GABA_B receptors in the RVLM. While it is older than others, the study is important to understand the history of the microinjection technique and the previous investigations of the GABA receptors in the RVLM. At the time of the study, the GABA_B antagonists (2-OH-s and CGP-35348) had just been created, allowing the study to research whether or not the GABA_B receptors were present in the rostral ventrolateral medulla (RVLM). Additionally, Avanzino et al. wanted to determine whether or not GABA_B receptors contribute to the regulation of the sympathetic nervous system output (which the researchers call the central cardiovascular regulation).

The animals were paralyzed and artificially respirated after the first round of microinjections to control for any respiratory changes during the measurements. Heart rate and blood pressure were measured during the microinjection experiments. The researchers assumed that if the GABA_B receptors were present in the RVLM, the antagonists would produce an increase in the blood pressure and heart rate. Two different microinjections followed: 1. Rats received bilateral microinjections of one of the GABA_B receptor antagonists or; 2. Rats received unilateral microinjections of the antagonist followed by either a GABA_A or GABA_B receptor agonists following the electrolytic lesion of the contralateral RVLM.

The first experiments produced increases in blood pressure and heart rate after the microinjections of either of the GABA_B receptor antagonists. These results held true after the rats were paralyzed, as well. The researchers concluded that the GABA_B receptors could be present in the RVLM and may contribute to the regulation of the central cardiovascular regulation. To further investigate this, the researchers injected the antagonists with either a GABA_B agonist or a GABA_A agonist. During this second experiment, the microinjections were completed unilaterally after the electrolytic lesion of the opposite RVLM. After the injections of 2-OH-s and CGP-35348, either badlofen (the GABA_B agonist) or muscimol (the GABA_A agonist) followed. Both of these agonists produced depressor responses when injected alone. However, the antagonists prevented the decrease in blood pressure only when injected with badlofen. The muscimol + antagonist injections were not significantly different to the muscimol alone. The same results were obtained in the paralyzed animals.

The results from the study suggested that GABA_B receptors are present in the RVLM in rats. These results are useful for future studies looking to further investigate the regulation of the RVLM in the central cardiovascular regulation. Additionally, the protocol of the experiment shows the significance of the microinjections. This experiment type is useful for studying the presence of receptors, and for investigating the function of brain regions, specifically the RVLM.

-LivInLaVida