5-HT2 receptor characteristics in frontal cortex and 5-HT2 receptor-mediated head-twitch behaviour following antidepressant treatment to mice

Abstract

The effects of repeated administration of antidepressant drugs or electroconvulsive shock on the binding of [3H]-spiperone to the 5-hydroxytryptamine 2 (5-HT2) receptor in mouse frontal cortex and the 5-HT-mediated head-twitch response have been examined. Repeated electroconvulsive shock increased both the head-twitch response and the number of 5-HT2 binding sites (Bmax). After 35 d but not 24 h or 14 d oral tranylcypromine (5.6 mg kg-1 per day) there was a marked decrease in both the behavioural response and the number of 5-HT2 receptors. Repeated oral doses of zimeldine (20 mg kg-1 per day, 14 days) also decreased the head-twitch response and the number of 5-HT2 binding sites and these effects persisted after 48 h withdrawal. Oral mianserin (2.1 mg kg-1 per day, 14 days) decreased both the behaviour and the number of 5-HT2 binding sites, but this change was also seen after acute (1 day) administration. After 48 h withdrawal from chronic treatment the head-twitch response was still decreased but the Bmax had returned to control values. Desipramine given orally (27 mg kg-1 per day, 14 days) decreased both the behaviour and number of 5-HT2 binding sites. After 48 h withdrawal, binding was still decreased but the head-twitch response was enhanced above control values. In contrast to repeated electroconvulsive shock (ECS), all drugs decreased both 5-HT2 binding and the head-twitch response, while the mice were still on treatment. Binding and behaviour did not correlate after withdrawal. It is concluded that antidepressant treatments do not produce a common alteration in 5-HT2 receptor number and function.