Possible role of alpha-2 and alpha-1 adrenoceptors in the experimentally-induced depression of the central nervous system.
The alpha-2 adrenoceptor agonists clonidine and xylazine were employed in chicks and rats to induce a loss of the righting reflex, a sign for depression of the central nervous system. These effects of clonidine and xylazine were antagonized by yohimbine, idazoxan and CH-38083 (7,8-(methylenedioxi)-14-alpha-hydroxyalloberbane HCl), compounds having alpha-2 adrenoceptor antagonist properties. Prazosin, an antagonist for alpha-1 adrenoceptors, enforced the alpha-2 adrenoceptor agonist-induced depression in both species. 6-Hydroxydopamine treatment, which reduced the norepinephrine concentrations in the rat cerebral cortex by 76%, increased the duration of the loss of righting reflex induced by xylazine indicating that central postsynaptic alpha-2 adrenoceptors might also be involved in this behavioral alteration. The electrically-stimulated tritium release was also determined from the isolated rat cerebral cortex slices which had been preloaded with 3H-norepinephrine. Clonidine and xylazine inhibited the stimulation-induced tritium release and this inhibition was counteracted by yohimbine, idazoxan or CH-38083, but not by prazosin. We have concluded from the present data that stimulation of alpha-2 adrenoceptors with pre- and postsynaptic locations or inhibition of alpha-1 adrenoceptors in the central nervous system may shift the depression/vigilance balance to the direction of depression which might be accompanied by a decreased activity of cortical noradrenergic neural transmission.
Harsing
L G
LG
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Kapocsi
J
J
Vizi
E S
ES
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002645:Chickens; D003000:Clonidine / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D013843:Thiazines / Q000494:pharmacology*; D014991:Xylazine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D006892:Hydroxydopamines; D013843:Thiazines; D014991:Xylazine; D016627:Oxidopamine; D003000:Clonidine; D009638:Norepinephrine