Reboxetine attenuates forced swim test-induced behavioural and neurochemical alterations in the rat

Connor, Thomas J.; Kelliher, Padraig; Harkin, Andrew; Kelly, J.P.; Leonard, B. E.

doi:10.1016/s0924-977x(99)80212-0

Cited by 5 publications

(6 citation statements)

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“…DalZotto et al (2000) have also demonstrated HPA axis activation following FST exposure as evidenced by a transient increase in ACTH. Administration of the selective norepinephrine reuptake inhibitor reboxetine, while significantly reducing immobility time and attenuating changes in brain monoaminergic activity, did not alter the corticosterone response to swim stress (Connor et al 1999). Similar results obtained following subacute administration of the norepinephrine reuptake inhibitor desipramine ) make it difficult to associate the behavioral effects of these antidepressants in the FST with changes in HPA axis activity.…”

Section: Discussionmentioning

confidence: 82%

“…It has been reported that extracellular levels of 5-HT remained unchanged in the frontal cortex after swim stress (Jordan et al 1994;Kirby et al 1995) although care must be taken when comparing extracellular levels of a neurotransmitter, which reflects the net sum of synthesis, release and re-uptake, with tissue levels of that neurotransmitter. Other studies have reported an FST-induced increase in 5-HT turnover in this region (Connor et al 1997(Connor et al , 1999. However, in the experiments of Connor et al, rats were exposed to a 15 min pre-test FST exposure 24 h prior to a 5 min test session.…”

Section: Discussionmentioning

confidence: 95%

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Behavioral, neuroendocrine and neurochemical effects of the imidazoline I2 receptor selective ligand BU224 in naive rats and rats exposed to the stress of the forced swim test

et al. 2003

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 95%

Behavioral, neuroendocrine and neurochemical effects of the imidazoline I2 receptor selective ligand BU224 in naive rats and rats exposed to the stress of the forced swim test

et al. 2003

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“…Reboxetine has been shown to attenuate stress responses. Forced swim test-induced behavioral and neurochemical alterations in rats have been attenuated by acute administration of reboxetine (20). Furthermore, chronic reboxetine treatment has attenuated behavioral consequences, and associated changes in GABA neurotransmission in rats exposed to mild variable stress (57).…”

Section: Behavioral Pharmacology Of Reboxetinementioning

confidence: 99%

The Selective Norepinephrine Reuptake Inhibitor Antidepressant Reboxetine: Pharmacological and Clinical Profile

et al. 2004

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Reboxetine is the first commercially available norepinephrine reuptake inhibitor developed specifically as a first line therapy for major depressive disorder. In vitro and in vivo pharmacological studies indicated that reboxetine methanesulphonate has high affinity and selectivity for the human norepinephrine transporter over the serotonin and dopamine transporters. Pharmacological specificity is further demonstrated by the absence of affinity for 45 transmitter receptors and CNS targets. Pharmacokinetic studies demonstrated that reboxetine is suitable for twice daily administration (8-10 mg/day) and that it exhibits minimal drug-drug interactions. The starting dose of reboxetine should be reduced in the elderly, in patients with renal or hepatic impairment, or in patients receiving potent CYP3A inhibitors. A total of 20 phase II/III clinical studies comprising placebo-controlled, active comparator-controlled and open-label uncontrolled studies in both short-term and long-term treatment of major depression have been conducted. In the treatment of major depression, reboxetine was superior to placebo in 5 of 12 short- or long-term placebo-controlled studies and was comparable in efficacy to active comparators in 3 out of 3 active-controlled studies. Unlike conventional tricyclic antidepressants (TCAs), reboxetine had only minimal sedative and cardiovascular liabilities, probably due to increased pharmacological specificity of reboxetine as compared with TCAs. Unlike serotonin reuptake inhibitors, this selective and specific norepinephrine reuptake inhibitor demonstrated a distinct side-effect profile with diminishing sexual dysfunction and GI side effects. The availability of this agent has afforded patients suffering from major depressive disorder a new class of agents to combat the debilitating consequence of this psychiatric disease. The demonstrated pharmacological specificity of this compound has provided the psychopharmacology community with a tool to elucidate the role of norepinephrine in brain functions. Testing this agent in different animal models has enabled the exploration of the role of modulation of norepinephrine tone in the therapy of CNS disorders beyond depression.

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“…The doses of reboxetine and desipramine were chosen based on the pharmacological activity of these compounds in behavioural tests of anti-depressant action (Connor et al 1998(Connor et al , 1999Harkin et al 1999b). The dose of yohimbine was chosen based on its ability to antagonize the hypothermic response to clonidine, a model of central α 2 -adrenoceptor function (O'Donnell et al 1996).…”

Section: Determination Of Brain Biogenic Amine Concentrationsmentioning

confidence: 99%

Modulation of MK-801-induced behaviour by noradrenergic agents in mice

et al. 2001

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Rationale: Inhibition of glutamatergic Nmethyl-D-aspartate (NMDA) receptors following the administration of NMDA receptor antagonists results in psychotic-like behaviour. Whereas it is known that pharmacological manipulation of dopaminergic and serotonergic pathways affect this drug-induced psychosis, a role for noradrenaline has not yet been clearly defined. Objectives: Thus, in the present study, we assessed a possible role for noradrenaline in the behavioural response to the non-competitive NMDA receptor anatgonist, MK-801, in male CD-I mice. Results: MK-801 (0.02-1.28 mg/kg; ED 50 0.2 mg/kg; s.c.) induced a dosedependent increase in locomotor, stereotypic and ataxic behaviours. Pre-treatment with the noradrenaline re-uptake inhibitors, desipramine (10 mg/kg; i.p.) and reboxetine (20 mg/kg; i.p.), attenuated the locomotor, stereotypic and ataxic response to MK-801 (0.2 mg/kg; s.c.). The noradrenergic system was lesioned with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4, 50 mg/kg; i.p., 7 and 4 days prior to challenge) to reduce noradrenaline concentrations in the cortex by 70%-80%. Whereas DSP-4 lesioning had little effect on the response to MK-801, it completely reversed the attenuating effects of reboxetine. Pre-treatment with the α 2 adrenoceptor agonist, clonidine (0.2 mg/kg; i.p.), and the antagonist, yohimbine (2 mg/kg; i.p.), attenuated and potentiated the response to MK-801, respectively. Pre-treatment with the α 1 adrenoceptor antagonist, prazosin (2 mg/kg; i.p.), reduced the MK-801-induced response. Conclusions: It therefore appears that presynaptic noradrenergic α 2 and postsynaptic α 1 adrenoceptor stimulation exert opposing effects on the behavioural expression of MK-801 in mice.

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Reboxetine attenuates forced swim test-induced behavioural and neurochemical alterations in the rat

Cited by 5 publications

References 0 publications

Behavioral, neuroendocrine and neurochemical effects of the imidazoline I2 receptor selective ligand BU224 in naive rats and rats exposed to the stress of the forced swim test

Behavioral, neuroendocrine and neurochemical effects of the imidazoline I2 receptor selective ligand BU224 in naive rats and rats exposed to the stress of the forced swim test

The Selective Norepinephrine Reuptake Inhibitor Antidepressant Reboxetine: Pharmacological and Clinical Profile

Modulation of MK-801-induced behaviour by noradrenergic agents in mice

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