| Abstract: | It is possible to induce sub- and super-sensitivity of β-adrenergic receptors by long-term treatment with drugs acting on catecholamine systems. In contrast, analogous treatment with drugs acting on serotoninergic systems does not modify serotonin receptor sensitivity as measured by serotonin binding. Firstly, chronic 1-5HTP, the precursor amino acid, increases serotonin turnover but does not decrease serotonin binding. Secondly, chronic clomipramine, a predominantly serotonin uptake inhibitor also has no effect on serotonin binding. Thirdly, chronic metergoline, a selective serotonin antagonist in the cortex, does not induce supersensitivity.This apparent intractability of the serotonin receptor to changes after long-term treatment indicates a different post-synaptic regulatory mechanism than that found in catecholaminergic neurones. Furthermore, modification of serotonin receptor sensitivity is probably not relevant to the mode of action of antidepressant drugs. Rather, the response of pineal melatonin stimulation found after chronic clomipramine in these experiments implicates induction of β-receptor subsensitivity. |
