FUNCTIONAL ANALYSES OF ALPHA(1)-ADRENOCEPTOR SUBTYPES IN RAT HYPOTHALAMIC VENTROMEDIAL NUCLEUS NEURONS

Activation of alpha(1)-adrenoceptors in rat hypothalamic ventromedial nucleus can excite neurons and facilitate female sexual behavior. To identify the alpha(1)-adrenoceptor subtype(s) involved, the alpha(1B)-adrenoceptor-specific antagonist chloroethylclonidine (100 mu M) and/or the alpha(1A)-adrenoceptor-selective antagonist 5-methyl urapidil (1 or 2.5 mu M) or WB-4101 (0.1-10 mu M) were applied to a recording chamber bathing the hypothalamic slice containing the ventromedial nucleus. In all the neurons tested, both types of antagonists blocked, often completely, excitatory responses to nonselective alpha(1)-adrenoceptor agonists. Since the doses used were unlikely to make these antagonists nonselective, the results suggest that activation of both alpha(1A)- and alpha(1B)-adrenoceptor subtypes was necessary for alpha(1)-adrenoceptor agonists to evoke an excitation, or that with the present application method - injection into the continuously perfused chamber - chloroethylclonidine did not act specifically. In preincubation (at 37 degrees C for 90 min) where it was reported to act by specific alkylation, chloroethylclonidine (100 mu M) but not the vehicle abolished the excitation evoked by an alpha(1)-adrenoceptor agonist, but not that by carbachol or other excitants. Also, either in bath application or incubation, chloroethylclonidine worked equally efficiently on slices from ovariectomized rats, that reportedly contain few alpha(1)-adrenoceptors, and from those treated with estrogen which induces alpha(1B)-adrenoceptors selectively, suggesting that alpha(1B)-adrenoceptor was necessary even when in low abundance. Thus, it is likely that the activation of both alpha(1A)- and alpha(1B)-adrenoceptor subtypes and also thereby, their respective couplings to second messengers are necessary to mediate the actions of alpha(1)-adrenoceptor agonists in exciting hypothalamic neurons.