Effects of antidepressant drugs and GR 205171, an neurokinin-1 (NK1) receptor antagonist, on the response in the forced swim test and on monoamine extracellular levels in the frontal cortex of the mouse

Zocchi, Alessandro; Varnier, Giorgia; Arban, Roberto; Griffante, Cristiana; Zanetti, Lara; Bettelini, L.; Marchi, Mario; Gerrard, Philip; Corsi, Mauro

doi:10.1016/s0304-3940(03)00305-7

Cited by 62 publications

(39 citation statements)

References 17 publications

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“…1, D and F). These results concur with recent microdialysis experiments performed in awake mice (Zocchi et al, 2003;Guiard et al, 2004), suggesting a lack of tonic regulation of 5-HT transmission by SP. It is noteworthy that NK1 receptor antagonists have been reported to be efficient anxiolytic and antidepressant agents in several animal models (Chahl, 2006).…”

Section: Resultssupporting

confidence: 92%

Substance P Neurokinin 1 Receptor Activation within the Dorsal Raphe Nucleus Controls Serotonin Release in the Mouse Frontal Cortex

Guiard

Guilloux²,

Repérant³

et al. 2007

Mol Pharmacol

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Preclinical studies suggest that substance P (SP) neurokinin 1 (NK1) receptor antagonists are efficient in the treatment of anxiety and depression. This therapeutic activity could be mediated via stimulation of serotonin (5-HT) neurons located in the dorsal raphe nucleus (DRN), which receive important SP-NK1 receptor immunoreactive innervations. The present study examined the effects of intraraphe injection of SP on extracellular 5-HT levels in the frontal cortex, ventral hippocampus, and DRN by using intracerebral microdialysis in conscious mice. Intraraphe SP injection dose dependently decreased cortical 5-HT release, whereas no effects were detected in the ventral hippocampus. Cortical effects were blocked by the selective NK1 receptor antagonist N- [[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methyl]-2-phenylpiperidin-3-amine (GR205171) and completely dampened in mice lacking NK1 receptors. Furthermore, genetic (in knockout 5-HT 1A Ϫ/Ϫ mice) or pharmacological inactivation of 5-HT 1A autoreceptors blocked cortical responses to SP. Contrasting with its cortical effects, intraraphe SP injection increased 5-HT outflow in the DRN in wild-type mice; this effect was potentiated by a local perfusion of the selective 5-Finally, SP-induced changes in frontal cortex and DRN dialysate 5-HT levels were blocked by the DRN perfusion of the ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate ionotropic receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). These data support the hypothesis that SP-induced overactivation of 5-HT 1A autoreceptors within the DRN limits cortical 5-HT release. A better knowledge of the complex relationship between tachykininergic, serotonergic, and glutamatergic systems within the DRN might help better understand the pathophysiology and subsequent treatment of depression.Substance P (SP), a small peptide that belongs to the tachykinins family with neurokinins A and B, is widely distributed in the brain, specifically in limbic regions and brainstem nuclei such as the dorsal raphe nucleus (DRN) (Froger et al., 2001;Commons et al., 2002;Lacoste et al., 2006). In several species, including rodents and humans, SP distribution overlaps with that of its high-affinity NK1 receptor (Ribeiro-da-Silva and Hokfelt, 2000). Recent clinical and preclinical studies have pointed out the potential therapeutic action of SP (neurokinin 1) receptor antagonists in major depressive disorders (Kramer et al., 1998;Chahl, 2006). Data obtained from NK1 receptor knockout mice have suggested that the antidepressant-like action of NK1 receptor inactivation may result, at least in part, from an increase in central 5-HT neurotransmission through functional desensitization B.P.G. was the recipient of a fellowship from La Fondation pour la Recherche Medicale (FRM) during the performance of this work.Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org. doi:10.1124/mol.107.040113.ABBREVIATIONS: SP, substance P; DRN, dorsal raphe nucleus; NK,...

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Section: Resultssupporting

confidence: 92%

Substance P Neurokinin 1 Receptor Activation within the Dorsal Raphe Nucleus Controls Serotonin Release in the Mouse Frontal Cortex

Guiard

Guilloux²,

Repérant³

et al. 2007

Mol Pharmacol

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“…Moreover, we could show similar behavioral effects after systemic administration of L-822429, indicating that the modulatory action within the LS is a critical component for stress-coping modulation by systemic treatment with NK1R antagonists. Our data confirm previous findings demonstrating similar antidepressant-like effects after acute systemic application of different NK1R antagonists in rats (Zocchi et al, 2003;Dableh et al, 2005) or genetic disruption of NK1R function in mice (Rupniak et al, 2001). While pharmacological antagonisms of NK1R in mice had no effect, it potentiated the antidepressant-like activity of various classical antidepressant agents in the forced swim test (Chenu et al, 2006).…”

Section: Effect Of Nk1r Blockade On Stress-coping Behaviorsupporting

confidence: 91%

“…Our data demonstrate for the first time immediate NK1R antagonist-induced elevation of extracellular 5-HT levels in the LS, a dorsal raphe terminal field that is known to play a crucial role in processing stress and anxiety reactions. It seems that the observed effect is regionally very discrete, since no facilitatory effects of NK1R antagonist on 5-HT efflux could be demonstrated in other 5-HT target areas such as the frontal cortex and hippocampus (Froger et al, 2001;Millan et al, 2001;Lejeune et al, 2002;Zocchi et al, 2003;Guiard et al, 2004Guiard et al, , 2006. The now observed action may be of relevance for the clinical evidence that NK1R antagonists exert therapeutic effects also after acute or short-time treatment (McLean, 2005).…”

Section: Behaviorally Significant Interaction Between Sp and 5-ht Sysmentioning

confidence: 76%

Neurokinin 1 Receptor Antagonism Promotes Active Stress Coping Via Enhanced Septal 5-HT Transmission

Ebner

Singewald

Whittle

et al. 2007

Neuropsychopharmacol

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Antagonists of the substance P (SP) preferring neurokinin 1 receptor (NK1R) represent a promising novel class of drugs for the treatment of stress-related disorders such as depression and anxiety disorders; however, the involved neuronal pathways releasing SP in response to stressors are ill defined. By using in vivo microdialysis in combination with a highly sensitive and selective radioimmunoassay we found that exposure to forced swim stress increased SP release in the rat lateral septum (LS), a key area in processing emotions and stress responses. Acute administration of the selective NK1R antagonist L-822429 injected either systemically or locally into the LS reduced passive and facilitated active stress-coping strategies in the forced swim test. This effect seems to be mediated by enhanced intraseptal serotonergic transmission via serotonin (5-HT)1A receptors since NK1R blockade reversed the swim stress-induced decrease to an increase in extracellular 5-HT efflux, and furthermore the behavioral effects of L-822429 were blocked by intraseptal 5-HT1A receptor antagonism. A direct heterosynaptic regulation by NK1R on 5-HT release from serotonergic fibers was ruled out by immunocytochemistry at the light and electron microscopic level indicating involvement of GABAergic interneuron(s) in this interaction. Taken together, our data identify the LS as a critical brain area for the involvement of SP transmission in the modulation of stress responses and demonstrate that NK1R blockade can elicit a functionally significant facilitatory effect on 5-HT transmission, which does not necessarily involve the previously proposed interaction with neuronal firing at the cell body level of raphe neurons.

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“…This hypothesis is strengthened by the putative role of dopamine and D 3 Rs in the regulation of mood (Maj et al, 1997;Willner, 1997;Lammers et al, 2000). Bupropion and nortriptyline, as well as other antidepressants such as imipramine, all have positive effects on performance in the forced swimming test (Porsolt et al, 1977;Steru et al, 1985;Zocchi et al, 2003), but D 3 R ligands have not been studied with this procedure. To address the issue of potential antidepressant effects of D 3 R ligands, we compared the effects of BP 897 and imipramine in the forced swimming test.…”

Section: Introductionmentioning

confidence: 99%

Dopamine D3 Receptor Ligands Block Nicotine-Induced Conditioned Place Preferences through a Mechanism that does not Involve Discriminative-Stimulus or Antidepressant-Like Effects

Foll

Sokoloff

Stark

et al. 2004

Neuropsychopharmacol

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Environmental stimuli previously paired with drug taking appear to play a critical role in nicotine dependence. Converging anatomical, pharmacological, and behavioral evidence implicates dopamine D 3 receptors (D 3 Rs) in the mechanisms underlying stimulus-controlled drug-seeking behavior. This study assessed the effects of BP 897, a D 3 R partial agonist and ST 198, a D 3 R antagonist, on nicotine-induced conditioned place preferences (CPPs), used as a measure of drug-seeking behavior, on food-maintained responding and on discrimination performance under a two-lever-choice nicotine discrimination procedure. BP 897 and ST 198 both blocked the expression of nicotine-induced CPP at doses selective for D 3 R. They had no effect on locomotor activity in the CPP apparatus and no significant effect on nicotine discrimination performance or food-maintained responding under the discrimination procedure. Involvement of antidepressant actions in the effects of BP 897 and ST 198 on CPP is unlikely, since we found no effect of D 3 R blockade with BP 897 or genetic depletion of D 3 Rs in a forced swimming test, used as a behavioral test for antidepressant activity. This suggests that D 3 R ligands reduce the motivational effects of nicotine by a mechanism distinct from those of nicotine replacement therapy and bupropion, the two currently used aids for smoking cessation in humans. These findings support the use of D 3 R ligands as aids for smoking cessation and indicate that their effects would be selective for those rewarding or reinforcing effects of nicotine that contribute to the maintenance of tobacco-smoking behavior, without affecting subjective responses to nicotine or producing any antidepressant-like effects.

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Effects of antidepressant drugs and GR 205171, an neurokinin-1 (NK1) receptor antagonist, on the response in the forced swim test and on monoamine extracellular levels in the frontal cortex of the mouse

Cited by 62 publications

References 17 publications

Substance P Neurokinin 1 Receptor Activation within the Dorsal Raphe Nucleus Controls Serotonin Release in the Mouse Frontal Cortex

Substance P Neurokinin 1 Receptor Activation within the Dorsal Raphe Nucleus Controls Serotonin Release in the Mouse Frontal Cortex

Neurokinin 1 Receptor Antagonism Promotes Active Stress Coping Via Enhanced Septal 5-HT Transmission

Dopamine D3 Receptor Ligands Block Nicotine-Induced Conditioned Place Preferences through a Mechanism that does not Involve Discriminative-Stimulus or Antidepressant-Like Effects

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