Goodwin GM, Green AR, Johnson P. 5-HT2 receptor characteristics in frontal cortex and 5-HT2 receptor-mediated head-twitch behaviour following antidepressant treatment to mice

British Journal of Pharmacology (Impact Factor: 4.84). 10/1984; 83(1):235-42. DOI: 10.1111/j.1476-5381.1984.tb10140.x
Source: PubMed


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.

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Available from: Guy Goodwin, Nov 10, 2015
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    • "This test was performed with modifications of the Goodwin et al. [14] procedure. The mice were administered with 5-HTP (200 mg/kg, i.p.) and placed in a cylindrical container (24 cm×15 cm×15 cm), with the head twitches of the mice counted for 10 min, starting 15 min after 5-HTP treatment. "
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    • "Electroconvulsive shock is an exception to the pattern of most antidepressant drugs in that an up-regulation of cortical 5-HT 2A receptors are found following chronic ECS treatment in rodents (Biegon and Israeli, 1987; Butler et al., 1993; Goodwin et al., 1984; Kellar and Bergstrom, 1983; Kellar et al., 1981; Pandey et al., 1992; Stockmeier and Kellar, 1986; Vetulani et al., 1981). The only robust widely replicated indirect change in 5-HT 2A receptor function following repeated daily administration of ECS is an enhancement of head shakes or head twitches induced by 5-HT 2A receptor agonists (Godfrey et al., 1988; Goodwin et al., 1984; Lebrecht and Nowak, 1980; Moorman et al., 1996). This head shake response induced by 5-HT 2A receptor agonists does appear to involve local 5-HT 2A receptors in the mPFC (Granhoff et al., 1992; Willins et al., 1997). "
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    • "Head twitches, rapid movements of the head with little or no involvement of the trunk (Goodwin et al. 1984), were counted visually with the use of a stopwatch between 30 and 35 min after the s.c. administration of DOI or saline. "
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