Withdrawal from chronic treatment with metergoline, dl-propranolol and amitriptyline enhances serotonin receptor mediated behaviour in the rat.

Acute treatment of rats with metergoline (2 mg/kg), a serotonin antagonist, prevented the behavioural syndrome produced by the serotonin agonist 5-methoxy-N',N'-dimethyltryptamine (2.5 mg/kg, 5MEODMT). dl-Propranolol (15 mg/kg) and amitriptyline (15 mg/kg) also inhibited the behavioural syndrome. The 5MEODMT behavioural syndrome was attenuated when metergoline or amitriptyline were administered daily for 14 days and 5MEODMT administered 30 min after the injection on day 14. This attenuation was not seen with chronic dl-propranolol treatment. When 5MEODMT was administered 72 h after the last injection of metergoline, amitriptyline or dl-propranolol on day 14, the behavioural syndrome was enhanced. The results suggest that withdrawal from chronic treatment with serotonin antagonists results in functional supersensitivity of serotoninergic neurones.