Inhibition of head twitch response to quipazine in rats by chronic amitriptyline but not fluvoxamine or citalopram

Chronic (twice daily/14 days), but not acute, treatment with 10 mg/kg PO amitriptyline reduced the number of quipazine (5 mg/kg)-induced head twitches in rats, measured 2 h (but not 72 h) after the last administration of the drug. Similar treatment with fluvoxamine or citalopram, which are more potent and much more specific serotonin uptake inhibitors than amitriptyline, did not affect the quipazine-induced response. In acute experiments, fluvoxamine (10 mg/kg PO) and citalopram (10 mg/kg PO) potentiated the head twitch reaction induced by l-5-hydroxytryptophan (50 mg/kg IP) given together with Ro 4-4602 (25 mg/kg IP), a peripheral decarboxylase inhibitor. Amitriptyline (10 mg/kg PO) slightly decreased the number of l-5-hydroxytryptophan (5-HTP)-induced head twitches. Higher doses of amitriptyline (20–40 mg/kg PO) also inhibited the quipazine-induced head twitch reaction. The brain level of amitriptyline measured 0.5–24 h after the last oral administration of the chronic dose of 10 mg/kg was always much higher than that observed at the same time intervals after an acute oral dose of 20 or 40 mg/kg. The results obtained indicate that a postsynaptic rather then presynaptic mechanism is responsible for the development of subsensitivity of the central serotonin receptors in the course of chronic treatment with amitriptyline.