Research articleNicotine enhances GABAergic inhibition of oxytocin mRNA-expressing neuron in the hypothalamic paraventricular nucleus in vitro in rats

- Nicotine inhibited PVN OT-mRNA expressing neuron in a dose-dependent manner.
- GABAA blocker abolished the nicotine-induced inhibition of OT neuron.
- Nicotine increased sIPSPs frequency of OT-mRNA expressing neurons.
- Nicotine modulated PVN OT secretion via enhancement of presynaptic GABA release.

We recently found that extracellular administration of nicotine indirectly excited hypothalamic paraventricular nucleus (PVN) corticotropin-releasing hormone (CRH) mRNA-expressing neurons. In this study, we studied the effect of nicotine on PVN oxytocin (OT) mRNA-expressing neuron in vitro in rats, by whole-cell patch-clamp recording technique, immunohistochemistry methods and single-cell reverse-transcription multiplex polymerase chain reaction (SC-RT-mPCR) methods Our results showed that 79.3% (73/92) of the 92 PVN putative magnocellular neurons co-expressed GAPDH mRNA and OT mRNA. Under current-clamp recording conditions, local micro application of nicotine (1-300 μM) induced a decrease in spontaneous firing rate accompanied with a hyperpolarization of membrane potential in 76.7% (56/73) of PVN OT mRNA-expressing magnocellular neurons. The nicotine induced inhibition in spontaneous activity of PVN OT mRNA-expressing magnocellular neurons was dose-dependent. The half-inhibitory concentration (IC50) is 2.9 μM. The nicotine induced hyperpolarization of PVN OT mRNA-expressing magnocellular neurons was sensitive to GABAA receptor antagonist, SR95531 (10 μM) and tetrodotoxin (TTX, 1 μM). In addition, local micro application of nicotine induced a significant increase in frequency of spontaneous inhibitory postsynaptic potentials (sIPSPs), but without changes in the sEPSPs amplitude of the OT-mRNA expressing neurons. Biocytin staining confirmed that the nicotine-sensitive OT-mRNA expressing neurons were the PVN magnocellular neurons. These results demonstrated that nicotine enhances the GABAergic inhibition, resulting in a decrease in spontaneous firing rate of the PVN OT-mRNA expressing neurons. These findings suggested that nicotine modulated PVN OT secretion via enhancement of both presynaptic action potential drive and quantal GABA release.