Mediation of the antidepressant‐like effect of 8‐OH‐DPAT in mice by postsynaptic 5‐HT_1A receptors

Abstract

1 The 5-hydroxytryptamine (5-HT),A agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) has been evaluated in a mouse model for detecting potential antidepressants (Porsolt test). The effects of various receptor antagonists, lesions of brain monoaminergic neurones and chronic drug treatments on this 8-OH-DPAT-induced response have also been determined. ) and opiate receptors (naloxone; 3-100 mg kg-', p.o.) had no effect on the 8-OH-DPAT response. 5 Selective destruction of 5-HT neurones with 5,7-dihydroxytryptamine or inhibition of 5-HT synthesis with p-chlorophenylalanine did not change the 8-OH-DPAT response in the Porsolt test. This response was also unaltered by pretreatment with the noradrenergic neurotoxin, DSP-4. 6 Administration of 8-OH-DPAT (3 mg kg-', s.c.) twice-daily for 10 days attenuated the hypothermia, but not the increased mobility, induced by 8-OH-DPAT (3 mg kg-', s.c.). Similarly, repeated administration of amitriptyline (3-30 mg kg-'), desipramine (3-30 mg kg-') or dothiepin (10-I00 mg kg-) also attenuated the former, but not the latter, response. 7 We conclude that 8-OH-DPAT produces an antidepressant-like effect in the Porsolt test which is mediated via postsynaptic 5-HTA receptors.

Dose-dependent noradrenergic and serotonergic properties of venlafaxine in animal models indicative of antidepressant activity

“…E¤ects include hypothermia in both mice and rats (Goodwin et al 1985;Hjorth 1985), a characteristic 5-HT syndrome in rats (Tricklebank et al 1984) and alterations in rat feeding behaviour (Hutson et al 1988). It has been shown that treatment with the serotonergic neurotoxins 5,7-DHT or PCPA, which are thought to act presynaptically, had no e¤ect on the anti-immobility response of 8-OH-DPAT with mice in the forced swimming test, indicating that the 5-HT 1A receptors mediating increased mobility are located postsynaptically (Luscombe et al 1993). Further evidence includes the fact that repeated administration of 8-OH-DPAT to mice does not modify its anti-immobility e¤ects in the forced swimming test, but has been shown rapidly to down-regulate the hypothermic response, which is thought to be mediated by presynaptic 5-HT 1A receptors (De Souza et al 1986;Luscombe et al 1989;Martin and Heal 1991).…”

Antidepressant-like effects of Trichilia catigua (Catuaba) extract: evidence for dopaminergic-mediated mechanisms

“…The immobility time was measured as described before. All the doses of inhibitors were selected on the basis of literature data (Luscombe et al 1993;Saddi and Abbott 2000;Nakamura and Tanaka 2001;Wiley and Martin 2003;Russig et al 2004). The chronic treatment with PCPA produced a 70% depletion of serotonin brain levels (Page et al 1999;Gavioli et al 2004).…”

Role of 5-HT1A and 5-HT1B Receptors in the Mediation of Behavior in the Forced Swim Test in Mice

“…Singh and Lucki (1993) also showed that agonist efficacy at 5-HT 1A receptors correlated with the ability of compounds to reduced immobility in the FST in rats. 8-OH-DPAT also showed an-tidepressant-like effects in the mouse version of this test (Luscombe et al 1993). Furthermore, destruction of 5-HT terminal with 5,7,-DHT did not alter the response to 8-OHDPAT in the FST, suggesting that post-synaptic 5-HT 1A receptors not affected by the neurotoxin mediate this response (Luscombe et al 1993).…”