The NK1-receptor antagonist NKP608 has an antidepressant-like effect in the chronic mild stress model of depression in rats

Papp, Mariusz; Vassout, A.; Gentsch, C.

doi:10.1016/s0166-4328(00)00230-8

Cited by 76 publications

(27 citation statements)

References 9 publications

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“…Furthermore, neurokinin-1 receptor antagonists are active in animal models sensitive to antidepressants (Kramer et al, 1998;Papp et al, 2000). In the present study, behaviorally relevant doses of the neurokinin-1 receptor antagonist L-AT failed to generalize to the isoproterenol cue, suggesting that, although this drug produces antidepressant-like effects, it does not do so by directly or indirectly increasing the stimulation of central ␤1-adrenergic receptors.…”

Section: Antidepressants and Isoproterenol Discrimination 609contrasting

confidence: 48%

Effects of Antidepressants in Rats Trained to Discriminate Centrally Administered Isoproterenol

Crissman

O'Donnell²

2002

J Pharmacol Exp Ther

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Previous work has shown that the discriminative stimulus effects of centrally administered isoproterenol are mediated primarily via ␤1-adrenergic receptors. In the present study, this model was used to investigate the ability of antidepressant drugs displaying various pharmacological profiles to stimulate ␤1-adrenergic receptors in vivo; this was assessed by determining whether they substituted for the discriminative stimulus effects of isoproterenol. Rats were trained to discriminate centrally administered isoproterenol (10 g i.c.v.) from artificial cerebral spinal fluid using a water-reinforced, two-lever operant task (fixed ratio 10 schedule). After acquisition of the discrimination, drugs were tested for substitution (i.p.). The tricyclic antidepressants protriptyline and desipramine, the norepinephrine uptake inhibitor nisoxetine, the monoamine oxidase inhibitor phenelzine, and the atypical antidepressants bupropion, mirtazapine, and venlafaxine all produced greater than 90% isoproterenol-appropriate responding. The serotonin uptake inhibitor fluoxetine, the atypical antidepressants buspirone and trazodone, and the novel, putative antidepressants N G -nitro-Larginine and N-acetyl-L-tryptophan 3,5-bis benzyl ester failed to substitute for isoproterenol at the dose ranges tested. Antagonism studies carried out with betaxolol for those drugs that fully generalized to isoproterenol's cue verified mediation by ␤1-adrenergic receptors. The present results indicate that drugs with noradrenergic activity generalize to isoproterenol's discriminative stimulus. Although this suggests a role for central ␤1-adrenergic receptors in the mechanism of action of certain antidepressant drugs, it does not seem that stimulation of these receptors is an effect shared by antidepressants from all pharmacological classes.Substantial research has implicated ␤-adrenergic receptors in the mechanism of action of antidepressant drugs. Stimulation of either ␤1-or ␤2-adrenergic receptors is sufficient to produce antidepressant-like effects on behavior in animal models such as learned helplessness, the forced-swim test, and differential-reinforcement-of-low rate (DRL) behavior (Martin et al., 1986;Finnegan et al

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Section: Antidepressants and Isoproterenol Discrimination 609contrasting

confidence: 48%

Effects of Antidepressants in Rats Trained to Discriminate Centrally Administered Isoproterenol

Crissman

O'Donnell²

2002

J Pharmacol Exp Ther

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“…For example, the NK1 an-tagonists, FK-888 and WIN51,708, were shown to have anxiolytic-like effects in the mouse and rat elevated plus-mazes, respectively (Teixeira et al 1996;Nikolaus et al 1999). Further, some recent publications have described the anxiolytic-like effects of the NK1 antagonist, NKP-608, in the rat social interaction assay (File 2000;Vassout et al 2000), and the antidepressant effects of NKP-608 in the rat chronic mild stress paradigm (Papp et al 2000).…”

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confidence: 99%

The Gerbil Elevated Plus-maze II Anxiolytic-like Effects of Selective Neurokinin NK1 Receptor Antagonists

Varty¹

2002

Neuropsychopharmacology

106

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Neurokinin NK1 receptor antagonists may have therapeutic potential in the treatment of anxiety and depression. Species variants in the NK1 receptor result in reduced affinity 694,060,994,721 produced anxiolyticlike The tachykinin system, particularly the neurokinin NK1 receptor, may represent a new target for the treatment of a number of psychiatric disorders. Of greatest significance to the field, Kramer et al. (1998) described the anxiolytic and antidepressant effects of the NK1 antagonist, MK-869, in a 6-week clinical trial in patients diagnosed with co-morbid anxiety and depression. In the few studies that have assessed the anxiolytic-like and antidepressant-like effects of NK1 receptor antagonists in preclinical tests, results support the hypotheses that NK1 receptor blockade may have a role in the treatment of affective disorders. For example, the NK1 an-

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“…There are NK1 antagonists that have comparable affinity at rat and human NK1 receptors and have been tested in traditional models of anxiety and depression. Examples are NKP-608, which has been shown to have anxiolytic-like and antidepressant-like properties in social interaction and chronic mild stress models (File 2000;Papp et al 2000;Vassout et al 2000), and FK-888 and WIN51,708, which produced anxiolytic-like effects in mouse and rat elevated plus-mazes, respectively (Teixeira et al 1996;Nikolaus et al 1999). Furthermore, research using NK1 receptor knockout mice have shown that the deletion of the NK1 receptor results in a profile of reduced anxietylike behaviors in a number of models including elevated plus-maze, novelty suppressed feeding, and maternal separation-induced vocalizations (Rupniak et al 2000;Santarelli et al 2001).…”

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confidence: 99%

The Gerbil Elevated Plus-Maze I Behavioral Characterization and Pharmacological Validation

Varty¹

2002

Neuropsychopharmacology

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The NK1-receptor antagonist NKP608 has an antidepressant-like effect in the chronic mild stress model of depression in rats

Cited by 76 publications

References 9 publications

Effects of Antidepressants in Rats Trained to Discriminate Centrally Administered Isoproterenol

Effects of Antidepressants in Rats Trained to Discriminate Centrally Administered Isoproterenol

The Gerbil Elevated Plus-maze II Anxiolytic-like Effects of Selective Neurokinin NK1 Receptor Antagonists

The Gerbil Elevated Plus-Maze I Behavioral Characterization and Pharmacological Validation

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