Effects of antagonists at the NMDA receptor complex in two models of anxiety

Płaźnik, Adam; Palejko, W; Nazar, Maciej; Jessa, Maria

doi:10.1016/0924-977x(94)90299-2

Cited by 89 publications

(36 citation statements)

References 25 publications

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“…These behaviors are altered by administration of drugs that humans report are anxiolytic (eg diazepam; Barrett and DiMascio, 1966;McDowall et al, 1966;Zbinden and Randall, 1967) or anxiogenic (eg FG 7142;Dorow, 1987), and so these behaviors have been widely used in assays to evaluate the anxiety-modulating effects of drugs and other manipulations. Anxiolytic drugs increase, and anxiogenic drugs decrease exploration of the open arms of the elevated plus maze (Handley and Mithani, 1984;Pellow and File, 1986), the central region of an open field (Hughes, 1972;Stefanski et al, 1992;Plaznik et al, 1994;Simon et al, 1994), and the lighted compartment of a dark-light shuttle box (Crawley and Goodwin, 1980;Costall et al, 1989;Onaivi and Martin, 1989;Chaouloff et al, 1997). We now report that i.c.v.…”

Section: Introductionmentioning

confidence: 86%

Nociceptin/Orphanin FQ Increases Anxiety-Related Behavior and Circulating Levels of Corticosterone During Neophobic Tests of Anxiety

Fernandez

Misilmeri

Felger

et al. 2003

Neuropsychopharmacol

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Intracranial administration of nociceptin/orphanin FQ (N/OFQ) increases circulating concentrations of adrenocorticotrophic hormone and corticosterone in unstressed rats, and elevates the responsiveness of these hormones during mild stress. Furthermore, N/OFQ and its cognate receptor are both abundant in a variety of limbic nuclei, and stress exposure decreases neuronal N/OFQ content in forebrain neurons. In light of these and other findings, we examined the potential involvement of N/OFQ in regulation of anxiety-related behaviors in rats. In the open field, elevated plus maze, and dark-light neophobic tests, intracerebroventricular N/OFQ (1.0 pmole-1.0 nmole) increased the expression of anxiety-related behaviors. Specifically, N/OFQ increased the latency to enter, decreased the number of entries into, and decreased the time spent in the exposed or brightly lit environments of all three tests. N/OFQ also enhanced thigmotactic responses in the open field test. The effects of diazepam and of the benzodiazepine inverse agonist FG 7142 were also assessed in independent groups of rats. In all three tests, the behavioral effects of N/OFQ resembled the anxiogenic actions of FG 7142, and contrasted with the anxiolytic actions of diazepam. N/OFQ administration also increased circulating concentrations of corticosterone during anxiety testing, in comparison with the concentrations in vehicle-treated controls. We conclude that N/OFQ administration is anxiogenic, and elevates responsiveness of the hypothalamic pituitary-adrenal axis during neophobic tests of anxiety. This supports the possibility that N/OFQ neurotransmission participates in processing of emotionally-salient and stressful stimuli, and suggests that normal functioning of the N/OFQ system may be important in physiological and psychological well-being.

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Section: Introductionmentioning

confidence: 86%

Nociceptin/Orphanin FQ Increases Anxiety-Related Behavior and Circulating Levels of Corticosterone During Neophobic Tests of Anxiety

Fernandez

Misilmeri

Felger

et al. 2003

Neuropsychopharmacol

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“…In light of this, there is increasing recognition that glutamatergic mechanisms may be a potential avenue to develop new treatment for anxiety problems such as panic disorder (for review, see Gorman, 2003;Millan, 2003). Some studies have demonstrated that the noncompetitive NMDA antagonist MK-801 (Xie and Commissaris, 1992;Xie et al, 1995), the competitive NMDA antagonist AP-7 (Plaznik et al, 1994), or metabotropic glutamate receptor agonists that reduce glutamate neurotransmission (Helton et al, 1998;Klodzinska et al, 1999;Kellner et al, 2005) reduce anxiety-like and panicassociated behavior in rats. These results and the present results suggest that selective glutamatergic receptor agents may be potential therapeutic strategies in treating panic disorder in humans.…”

Section: Discussionmentioning

confidence: 99%

Panic-Prone State Induced in Rats with GABA Dysfunction in the Dorsomedial Hypothalamus Is Mediated by NMDA Receptors

Johnson

Shekhar

2006

J. Neurosci.

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“…It has recently been proposed that glutamatergic system plays an important role in the pathophysiology of anxiety (Chojnacka-Wojcik et al, 2001;Wroblewski and Danysz, 1989). Different functional N-methyl-D-aspartate (NMDA) receptor antagonists exhibit anxiolytic-like activity in animal models (Bennett and Amrick, 1986;Corbett and Dunn, 1993;Plaznik et al, 1994;Przegalinski et al, 1996;Trullas et al, 1989;Winslow et al, 1990). The potential clinical use of NMDA receptor antagonists has been limited due to their undesirable side effects, such as muscle relaxation, ataxia, amnesia, and psychotomimetic effects (Scatton, 1993).…”

Section: Introductionmentioning

confidence: 99%

In the Amygdala Anxiolytic Action of mGlu5 Receptors Antagonist MPEP Involves Neuropeptide Y but not GABAA Signaling

Wierońska

Śmiałowska

Brański

et al. 2003

Neuropsychopharmacol

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Several lines of evidence indicate that inhibition of the metabotropic glutamate (mGlu) receptor 5 produces anxiolytic-like effects in rodents. Peptide neurotransmitter neuropeptide Y (NPY) produces an anxiolytic effect in rats after intraventricular or intra-amygdalar administration. Many classes of anxiolytic drugs exert their effect through the GABA-benzodiazepine (BZD) receptor complex. Therefore, in the present study we have investigated whether the anxiolytic action of MPEP (2-methyl-6-(phenylethynyl)pyridyne), an mGlu5 receptor antagonist, is mediated by a mechanism involving either the GABA-BZD receptor complex or NPY receptor. In the behavioral studies, the anxiolytic activity of MPEP (10 mg/kg, i.p.) was examined using plus-maze test. The BZD antagonist flumazenil (10 mg/kg, i.p.) was given to one group of rats and Y1 receptor antagonist BIBO 3304 (((R)-N- [[4-(aminocarbonylaminomethyl) phenyl] methyl]-N2-(diphenylacetyl)-argininamide trifluoroacetate)3304) (200 pmol/site, intra-amygdala) to the other. It was found that anxiolytic effects of MPEP were not changed by flumazenil, but were abolished by BIBO 3304. Immunohistochemical studies showed a high density of mGlu5 receptor immunoreactivity (IR) in the amygdala. The effect of MPEP on NPY expression in the amygdala was studied using immunohistochemistry (IH) and radioimmunoassay (RIA). Both methods showed a diminution of NPY IR expression, to about 43% (IH) or 81% (RIA) of the control level after multiple administrations, but we observed an increase up to 148% of the control after single MPEP administration. These effects may suggest a release of NPY from nerve terminals after MPEP administration. Our results indicate that the anxiolytic action of MPEP is conveyed through NPY neurons with the involvement of Y1 receptors in the amygdala and that BZD receptors do not significantly contribute to these effects.

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Effects of antagonists at the NMDA receptor complex in two models of anxiety

Cited by 89 publications

References 25 publications

Nociceptin/Orphanin FQ Increases Anxiety-Related Behavior and Circulating Levels of Corticosterone During Neophobic Tests of Anxiety

Nociceptin/Orphanin FQ Increases Anxiety-Related Behavior and Circulating Levels of Corticosterone During Neophobic Tests of Anxiety

Panic-Prone State Induced in Rats with GABA Dysfunction in the Dorsomedial Hypothalamus Is Mediated by NMDA Receptors

In the Amygdala Anxiolytic Action of mGlu5 Receptors Antagonist MPEP Involves Neuropeptide Y but not GABAA Signaling

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