Effects of chronic administration of antidepressant drugs on central serotonergic receptor mechanisms
Palgrave Macmillan UK eBooks – January 01, 1983
Source: OpenAlex
Summary
Chronic treatment with desipramine, imipramine, and zimelidine revealed significant behavioral changes linked to serotonin receptor sensitivity. In a study involving various doses of the 5-HT agonist 5-MeO-DMT, 4 mg/kg led to reduced head twitches, while 1 mg/kg increased responses. Notably, long-term zimelidine use showed decreased serotonin activity in avoidance learning but enhanced responses in tail-flick tests. Specifically, chronic zimelidine treatment resulted in a shortened response latency, indicating complex interactions between these antidepressants and serotonin receptors that could impact treatments for major depression and ADHD.
Abstract
The present studies have shown that chronic antidepressant treatment with desipramine (DMI), imipramine (IMI) and zimelidine produced behavioral evidence for sub- and supersensitivity depending on 5-HT agonist dose and types of behavior examined. Thus, chronic treatment with all three drugs reduced head twitches induced by a high dose of the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT, 4 mg/kg) while an enhanced response was observed at a low 5-MeO-DMT dose (1 mg/kg) or a low dose of the 5-HT precursor 1-5-hydroxytryptophan (12.5 mg/kg). Chronic ZIM and IMI treatment tended to enhance 5-HT receptor activity as assessed by the induction of hyperlocomotion by a high 5-MeO-DMT dose (4 mg/kg) while they reduced the effect of a low dose (1 mg/kg). Long-term ZIM treatment gave evidence of behavioral subsensitivity to the 5-HT agonist 5-MeO-DMT in avoidance learning, while an enhanced response to 5-MeO-DMT was observed in the tail-flick model. However, chronic ZIM treatment shortened response latency in the tail-flick model suggesting that the net result is a decrease in 5-HT activity.