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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    • "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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    ABSTRACT: A series of animal models are used to investigate the anti-depression mechanism of flavonoids in scutellariae radix (SR) in vivo. Depression-like behavior in mice was studied after intraperitoneal administration of SR. The results showed that SR administered to mice by the intraperitoneal route obviously shortened the duration in the tail suspension test and the forced swimming test, aggravated the symptoms of eyelid ptosis, akinesia, and mortality caused by reserpine, prolonged climbing times, affected the conditioned place preference, and increased sugar consumption in mice. However the SR did not affect the head twitches induced by 5-HTP, locomotor activity in mice, the toxicity of yohimbine, and the body temperature decrease caused by high dosage of apomorphine. The tests show that SR has some anti-depression effect related to the dopamine system. Furthermore another anti-depression mechanism was possible that could affect the mechanism of brain reward, bring positive reinforcement, and increase the sensitivity to euphoria in mice.
    Tsinghua Science & Technology 08/2010; 15(4-15):460-466. DOI:10.1016/S1007-0214(10)70088-2
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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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    ABSTRACT: Down-regulation of 5-hydroxytryptamine(2A) (5-HT(2A)) receptors has been a consistent effect induced by most antidepressant drugs. In contrast, electroconvulsive shock (ECS) up-regulates the number of 5-HT(2A) receptor binding sites. However, the effects of antidepressants on 5-HT(2A) receptor-mediated responses on identified cells of the cerebral cortex have not been examined. The purpose of the present study was to compare the effects of the tricyclic antidepressant imipramine and ECS on 5-HT(2A) receptor-mediated electrophysiological responses involving glutamatergic and GABAergic neurotransmission in the rat medial prefrontal cortex (mPFC) and piriform cortex, respectively. The electrophysiological effects of activating 5-HT(2A) receptors were consistent with 5-HT(2A) receptor binding regulation for imipramine and ECS except for the mPFC where chronic ECS decreased the potency of 5-HT at a 5-HT(2A) receptor-mediated response. These findings are consistent with the general hypothesis that chronic antidepressant treatments shift the balance of serotonergic neurotransmission towards inhibitory effects in the cortex.
    European Neuropsychopharmacology 08/2008; 18(7):498-507. DOI:10.1016/j.euroneuro.2008.01.003 · 4.37 Impact Factor
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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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    ABSTRACT: The serotonin reuptake transporter (SERT) helps to regulate brain serotonergic transmission and is the target of some antidepressants. To further understand SERT function, we measured a marker of regional brain phospholipase A2 (PLA2) activation in SERT knockout mice (SERT-/-) and their littermate controls (SERT+/+). Following administration of 1.5 mg/kg s.c. (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), a 5-HT(2A/2C) receptor agonist, to unanesthetized mice injected intravenously with radiolabeled arachidonic acid (AA), PLA2 activation, represented as the regional incorporation coefficient k* of AA, was determined with quantitative autoradiography in each of 71 brain regions. In SERT+/+ mice, DOI significantly increased k* in 27 regions known to have 5-HT(2A/2C) receptors, including the frontal, motor, somatosensory, pyriform and cingulate cortex, white matter, nucleus accumbens, caudate putamen, septum, CA1 of hippocampus, thalamus, and hypothalamus. In contrast, DOI did not increase k* significantly in any brain region of SERT-/- mice. Head twitches following DOI, which also were measured, were robust in SERT+/+ mice but were markedly attenuated in SERT-/- mice. These results show that a lifelong elevation of the synaptic 5-HT concentration in SERT-/- mice leads to downregulation of 5-HT(2A/2C) receptor-mediated PLA2 signaling via AA and of head twitches, in response to DOI.
    Psychopharmacology 07/2005; 180(1):12-20. DOI:10.1007/s00213-005-2231-5 · 3.88 Impact Factor
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