Effect of chronic lithium administration on adrenoceptor binding and adrenoceptor regulation in rat cerebral cortex.
Lithium (Li) at a concentration, which exerts prophylactic effects in affective disorders is known to alter noradrenaline turnover and the beta-adrenoceptor-dependent cAMP accumulation. In the present study the action of chronic Li administration (at least 5 weeks) on agonist and antagonist binding to adrenoceptors and on the regulation of adrenoceptors was investigated in rat cerebral cortex. Li treatment caused a small but significant decrease in the number of beta-adrenoceptor binding sites by 10% (3H-dihydroalprenolol binding) leaving the number of alpha 1- and alpha 2-adrenoceptor binding sites (3H-prazosin and 3H-rauwolscine, respectively) unchanged. The affinity of the radioligands as well as the affinity of agonists to these binding sites were not altered. The up-regulation of beta-adrenoceptor binding sites produced by repeated reserpine injections was inhibited by 32% in rats treated concomitantly with Li, although the noradrenaline depleting effect of reserpine was not impaired. In contrast, Li treatment had no effect on the up-regulation of beta-adrenoceptor binding induced by 6-OH-dopamine, nor did it alter the beta-adrenoceptor down-regulation following chronic administration of desipramine. The up-regulation of alpha 1-adrenoceptor binding sites caused by reserpine or 6-OH-dopamine also remained unaffected by Li. It is concluded that chronic Li has limited effects on cortical adrenoceptors and their regulation. The inhibition of beta-adrenoceptor up-regulation caused by reserpine may reflect an action of Li on non-adrenergic systems rather than a general "stabilizing" effect on adrenoceptors proposed previously.
Gross
G
G
Pharmakologisches Institut, Universitätsklinikum Essen, Federal Republic of Germany.
Dodt
C
C
Hanft
G
G
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D004082:Dihydroalprenolol; D006892:Hydroxydopamines / Q000494:pharmacology; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013563:Sympathectomy, Chemical; D015016:Yohimbine / Q000378:metabolism
D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D004082:Dihydroalprenolol; D016627:Oxidopamine; D008094:Lithium; D003891:Desipramine; D011224:Prazosin