Subtypes of α 1 ‐ and α 2 ‐Adrenoceptors Mediating Noradrenergic Modulation of Spontaneous Inhibitory Postsynaptic Currents in the Hypothalamic Paraventricular Nucleus

Noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) play important roles in the regulation of neuroendocrine and autonomic functions. Previous reports show that noradrenaline increases the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in a subpopulation of type II neurones, acting via α 1 ‐adrenoceptors (ARs), but reduces this frequency in most type I and another subpopulation of type II neurones, via α 2 ‐ARs on presynaptic GABA neurones. Here, we identified the subtypes of α‐ARs mediating noradrenaline‐induced increases and decreases in the sIPSC frequency of PVN neurones, by using slice patch recordings from PVN neurones. In both type I and II neurones, the noradrenaline‐induced decrease in sIPSC frequency was completely blocked by BRL44408 (α 2A ‐AR antagonist) at 1–3 µ M , which is approximately 1/100 of its equilibrium dissociation constant (pA 2  = 8.0), but not by prazosin (20–100 µ M , α 2B/C ‐AR antagonist; pA 2  = 7.5). The effect of noradrenaline was mimicked by guanfacine (α 2A ‐AR agonist) with an EC 50 of 0.1 µ M . In type II neurones, the noradrenaline‐induced increase in sIPSC frequency was not blocked by any of the following antagonists: RS17053 (10 µ M , α 1A ‐AR antagonist), BMY7378 (2 µ M , α 1D ‐AR antagonist), prazosin (0.1 µ M , α 1 ‐AR antagonist; pA 2  = 10.5), or chloroethylclonidine (10 µ M , α 1B/D ‐AR antagonist). However, the effect of noradrenaline was blocked by higher concentrations of prazosin (1 µ M ) or RS17053 (100 µ M ), suggesting the involvement of α 1L ‐subtype, a low affinity form of α 1A ‐ARs. Collectively, our results indicate that the α 2A ‐, or α 1L ‐ARs on the GABA neurones mediate the noradrenaline‐induced decreases, or increases in the frequencies of the sIPSCs of PVN neurones, respectively.