A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test

Gigliucci, Valentina; Buckley, Kathleen Niamh; Nunan, John D.; O’Shea, Karen M.; Harkin, Andrew

doi:10.1016/j.pbb.2009.11.007

Cited by 30 publications

(23 citation statements)

References 63 publications

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“…Each activity monitor was equipped with a set of horizontal infrared beams, positioned 3 cm above the base of the cage to record the activity. The set of beams consisted of a 12 Â 7 beam matrix, forming a grid of 66 Â 2.54 cm 2 cells within the cage (Gigliucci et al, 2010). Activity was recorded as the number of times a beam changed from unbroken to broken.…”

Section: Locomotor Activitymentioning

confidence: 99%

“…As NMDA-R antagonists possess antidepressant properties, targets downstream of the receptor, such as nNOS may represent targets for antidepressant activity. In this regard, L-arginine-derived inhibitors of NOS, produce antidepressant activity in the forced swimming test (FST), a preclinical behavioural screening procedure sensitive to antidepressant activity (Gigliucci et al, 2010;Harkin et al, 2003;Harkin et al, 1999;Dhir and Kulkarni, 2011;Wegener and Volke, 2010). Genetic deletion of nNOS or treatment with NOS inhibitors (7-nitroindazole (7-NI) or 1-(2-trifluoro-methyl-phenyl) imidazole (TRIM)) prevents chronic mild stressor (CMS)-induced depression-related behavioural and cellular changes in mice, further confirming the antidepressant potential of NOS inhibition Zhou et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Small-Molecule Inhibitors at the PSD-95/nNOS Interface have Antidepressant-Like Properties in Mice

Doucet

Levine

Dev

et al. 2013

Neuropsychopharmacol

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Previous studies have demonstrated that nitric oxide (NO) synthase inhibitors are as efficacious as tricyclic antidepressants in preclinical antidepressant screening procedures and in attenuating behavioural deficits associated with animal models of depression. The N-methyl-D-aspartate receptor (NMDA-R) complex gates Ca 2 þ , which interacts with calmodulin to subsequently activate NO synthase. We hypothesised that uncoupling neuronal nitric oxide synthase (nNOS) from the NMDA-R through the scaffolding protein postsynaptic density protein 95 (PSD-95) would produce behavioural antidepressant effects similar to NO synthase inhibitors. Small-molecule inhibitors of the PSD-95/nNOS interaction, IC87201 (0.01-2 mg/kg) and ZL006 (10 mg/kg) were tested for antidepressant properties in tests of antidepressant activity namely the tail suspension and forced swim tests in mice. We now report that IC87201 and ZL006 produce antidepressant-like responses in the forced swimming test (FST) and tail suspension test (TST) following a single administration in mice. By contrast to the tricyclic antidepressant imipramine (25 mg/kg), the effects are not observed 1 h following drug administration but are apparent 24 and 72 h later. Furthermore prior exposure to the TST or FST is required in order to observe the antidepressantrelated activity. Similar delayed and sustained antidepressant-like effects were observed following TRIM (50 mg/kg) and ketamine (30 mg/kg) in the TST. The antidepressant-like effects of ZL006 also generalise to IC87201 in the TST. IC87201 was devoid of effects on locomotor activity and step-through latency in the passive avoidance cognition test. These data support the hypothesis that targeting the PSD-95/nNOS interaction downstream of NMDA-R produces antidepressant effects and may represent a novel class of therapeutics for major depressive disorders.

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Section: Locomotor Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Small-Molecule Inhibitors at the PSD-95/nNOS Interface have Antidepressant-Like Properties in Mice

Doucet

Levine

Dev

et al. 2013

Neuropsychopharmacol

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“…In contrast, c-PTIO administration into the PL reduced locomotor activity during the first minute of the open field test. However, similar effects have been previously described following systemic administration of both NOS inhibitors and imipramine (Heiberg et al 2002;Harkin et al 2003;Gigliucci et al 2010). Since this reduction in the immobility period, the FST was seen after the same dose of c-PTIO, this Fig.…”

Section: Discussionsupporting

confidence: 82%

“…Os (Harkin et al, 2003;Volke et al, 2003;Gigliucci et al, 2010) e que se mostra dissociado dos efeitos comportamentais, visto que não leva a um aumento do tempo de imobilidade dos animais tratados com essas drogas no CPFMv-PL e expostos ao teste do nado forçado. A administração sistêmica de outros inibidores da NOS, como 7-NI e L-NNA, L-NAME e L-NMMA, também apresentou efeitos do tipo antidepressivo no TNF que são independentes de alterações motoras, de tal modo confirmando que os inibidores da NOS não agem como psicoestimulantes (Harkin et al, 1999;.…”

Section: Discussão Experimentos Com Injeção Central De Drogasunclassified

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Participação da via NMDA-NO do córtex pré-frontal medial ventral na modulação das consequências comportamentais do estresse de nado forçado: mecanismos intracelulares

Pereira¹

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A minha orientadora, professora Dr a . Sâmia Regiane Lourenço Joca, por todo apoio e confiança em mim depositados e, principalmente, pela excelente orientação.Ao professor Dr. Francisco Silva Guimarães, pelas discussões em seminários e pelo espaço cedido em seu laboratório.Ao professor Dr. Leonardo Resstel, pelo apoio, discussões e conselhos sobre o projeto, sem esquecer os churrascos muito bem preparados por ele.Ao professor Dr. Gregers Wegener, da Universidade de AarhusDinamarca, por ter me aceitado para realização de estágio no exterior em seu laboratório e por todo aprendizado obtido nessa excelente oportunidade.Ao Vinicius Sato, grande amigo do laboratório e de todo meu tempo em Ribeirão Preto, pela ajuda, pelas conversas e discussões.Aos amigos e amigas do laboratório, Laura A. S., Laura L., Cassiano, Karina, Ariandra, Deidiane, Murilo, Rafaela, Izaque e Aline pela ótima convivência.À nossa técnica do laboratório Flávia Sallata, pela ajuda no dia a dia do laboratório. Aos técnicos José Carlos e Eleni, do laboratório do professor Francisco S. Guimarães, por toda a ajuda.As secretárias Sonia, Fátima, Marlene e ao José Waldik Ramon por todos os esclarecimentos, ajuda com documentação e também pelos conselhos. A dona Nina por toda a ajuda no laboratório.

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Effects of S‐citalopram, citalopram, and R‐citalopram on the firing patterns of dopamine neurons in the ventral tegmental area, N‐methyl‐D‐aspartate receptor‐mediated transmission in the medial prefrontal cortex and cognitive function in the rat

Schilström

Konradsson-Geuken

Ivanov

et al. 2010

Synapse

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Escitalopram, the S-enantiomer of citalopram, possesses superior efficacy compared to other selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depression. Escitalopram binds to an allosteric site on the serotonin transporter, which further enhances the blockade of serotonin reuptake, whereas R-citalopram antagonizes this positive allosteric modulation. Escitalopram's effects on neurotransmitters other than serotonin, for example, dopamine and glutamate, are not well studied. Therefore, we here studied the effects of escitalopram, citalopram, and R-citalopram on dopamine cell firing in the ventral tegmental area, using single-cell recording in vivo and on NMDA receptor-mediated currents in pyramidal neurons in the medial prefrontal cortex using in vitro electrophysiology in rats. The cognitive effects of escitalopram and citalopram were also compared using the novel object recognition test. Escitalopram (40-640 μg/kg i.v.) increased both firing rate and burst firing of dopaminergic neurons, whereas citalopram (80-1280 μg/kg) had no effect on firing rate and only increased burst firing at high dosage. R-citalopram (40-640 μg/kg) had no significant effects. R-citalopram (320 μg/kg) antagonized the effects of escitalopram (320 μg/kg). A very low concentration of escitalopram (5 nM), but not citalopram (10 nM) or R-citalopram (5 nM), potentiated NMDA-induced currents in pyramidal neurons. Escitalopram's effect was antagonized by R-citalopram and blocked by the dopamine D(1) receptor antagonist SCH23390. Escitalopram, but not citalopram, improved recognition memory. Our data suggest that the excitatory effect of escitalopram on dopaminergic and NMDA receptor-mediated neurotransmission may have bearing on its cognitive-enhancing effect and superior efficacy compared to other SSRIs in major depression.

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A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test

Abstract: The present study determined regional serotonin (5-HT) synthesis and metabolism changes associated with the nitric oxide synthase (NOS)

Cited by 30 publications

References 63 publications

Small-Molecule Inhibitors at the PSD-95/nNOS Interface have Antidepressant-Like Properties in Mice

Small-Molecule Inhibitors at the PSD-95/nNOS Interface have Antidepressant-Like Properties in Mice

Participação da via NMDA-NO do córtex pré-frontal medial ventral na modulação das consequências comportamentais do estresse de nado forçado: mecanismos intracelulares

Effects of S‐citalopram, citalopram, and R‐citalopram on the firing patterns of dopamine neurons in the ventral tegmental area, N‐methyl‐D‐aspartate receptor‐mediated transmission in the medial prefrontal cortex and cognitive function in the rat

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