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 i dentify the alpha(1)-adrenoceptor subtype(s) involved, the alpha(1B)-a drenoceptor-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 cham ber 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 antagonist s nonselective, the results suggest that activation of both alpha(1A)- and alpha(1B)-adrenoceptor subtypes was necessary for alpha(1)-adreno ceptor agonists to evoke an excitation, or that with the present appli cation method - injection into the continuously perfused chamber - chl oroethylclonidine did not act specifically. In preincubation (at 37 de grees C for 90 min) where it was reported to act by specific alkylatio n, chloroethylclonidine (100 mu M) but not the vehicle abolished the e xcitation evoked by an alpha(1)-adrenoceptor agonist, but not that by carbachol or other excitants. Also, either in bath application or incu bation, chloroethylclonidine worked equally efficiently on slices from ovariectomized rats, that reportedly contain few alpha(1)-adrenocepto rs, and from those treated with estrogen which induces alpha(1B)-adren oceptors selectively, suggesting that alpha(1B)-adrenoceptor was neces sary even when in low abundance. Thus, it is likely that the activatio n of both alpha(1A)- and alpha(1B)-adrenoceptor subtypes and also ther eby, their respective couplings to second messengers are necessary to mediate the actions of alpha(1)-adrenoceptor agonists in exciting hypo thalamic neurons.