Abstract

Selective lesions of serotonin neurons or inhibition of serotonin synthesis results in an increase in the number of [3H]dihydroalprenolol binding sites in several areas of rat brain. Previously, this increase in binding sites was interpreted as an increase in beta-adrenergic receptors. However, the lesion-induced increase in [3H]dihydroalprenolol is not accompanied by an increase in isoproterenol- or norepinephrine-stimulated cyclic AMP production. The increased binding of [3H]dihydroalprenolol is blocked by the addition of serotonin but not by the addition of norepinephrine or dopamine to the assays. Furthermore, the addition of metergoline, a serotonin antagonist, also blocked the increase in lesioned tissues. Thus, the lesion-induced increase in [3H]dihydroalprenolol binding appears to represent an increase in serotonergic binding sites. Among drugs with some selectivity for serotonin-1 receptor subtypes, trifluoromethylphenylpiperazine and RU-24929 were as effective as serotonin in blocking lesion-induced increases in [3H]dihydroalprenolol binding. However, 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT), spiperone, and mesulergine were either much less effective than serotonin or completely ineffective. Radioligand binding to serotonin-1A and serotonin-1B sites with [3H]8-OH-DPAT and 125I-cyanopindolol, respectively, after lesions of serotonin axons or depletion of serotonin was not increased, despite a marked increase in [3H]dihydroalprenolol binding in the same tissues. When tissues from control rats or rats with serotonin lesions were preincubated at 37 degrees for 10 min to remove endogenous serotonin bound to receptors, the binding of [3H]dihydroalprenolol in controls was increased to the level seen in lesioned tissues. Thus, [3H]dihydroalprenolol binds primarily to beta-adrenergic receptors in control membranes that are not preincubated; however, either preincubation of control tissues or serotonin depletion unmasks a serotonin-1 receptor subtype to which [3H]dihydroalprenolol binds in addition to the beta-adrenergic receptor.