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

Abstract

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.

Role of atypical opiates in OCD. Experimental approach through the study of 5-HT2A/C receptor-mediated behavior

“…Along these lines, acute inhibition of serotonin reuptake did not inhibit the specific (DOI-induced) 5-HT2A-related behavior. These results are consistent with reports showing that acute fluvoxamine potentiated 5-HTP-induced head-twitch response (Pawlowski and Melzacka 1986) and failed to modify the number of DOI-induced shakes (Kawakami et al 2005). Nevertheless, SSRIs have been proved to be effective after chronic treatment, where a reduction in 5-HT2 receptor responsivity may have occurred in animal models related to human OCD (Nurnberg et al 1997).…”

Antidepressant-like effects of a water-soluble extract from the culture medium of Ganoderma lucidum mycelia in rats

“…The stereotypical behavior is induced by the serotonin precursor 5-HTP via an increase of serotonin levels in the synaptic clefts [28] and the subsequent indirect activation of 5-HT 2A receptors [29]. This response has been reported to be enhanced by acute inhibition of 5-HT reuptake by SSRIs [30]. By contrast, DOI, which has an approximately equal affinity for 5-HT 2A , 5-HT 2B and 5-HT 2C receptors, is considered to induce a head-twitch response by a direct agonistic effect on 5-HT 2A receptors, because a DOI-induced head-twitch response is blocked by selective 5-HT 2A antagonists but not by 5-HT 2B/2C antagonists [29,31] and is not modified by SSRIs [17,31].…”