Effect of chronic lithium administration on adrenoceptor binding and adrenoceptor regulation in rat cerebral cortex

Summary

Lithium (Li) at a concentration, which exerts prophylactic effects in affective disorders is known to alter noradrenaline turnover and the β-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 β-adrenoceptor binding sites by 10% (³H-dihydroalprenolol binding) leaving the number of α₁- and α₂-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 β-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 β-adrenoceptor binding induced by 6-OH-dopamine, nor did it alter the β-adrenoceptor down-regulation following chronic administration of desipramine. The up-regulation of α₁-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 β-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.