Evaluation of the anxiolytic-like effect of NKP608, a NK1-receptor antagonist, in two rat strains that differ in anxiety-related behaviors

Vendruscolo, Leandro F.; Takahashi, Reinaldo Ν.; Brüske, Gustavo R.; Ramos, André

doi:10.1007/s00213-003-1545-4

Cited by 45 publications

(30 citation statements)

References 43 publications

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“…The elevated plus maze testing was carried out as described previously (Vendruscolo et al, 2003) during withdrawal, just before subsequent self-administration sessions. The apparatus had four elevated arms (52 cm above the floor), 50 cm long and 10 cm wide, set in a cross-like arrangement, with …”

Section: Elevated Plus Mazementioning

confidence: 99%

The NK1 Receptor Antagonist L822429 Reduces Heroin Reinforcement

Barbier

Vendruscolo

Schlosburg

et al. 2012

Neuropsychopharmacol

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Genetic deletion of the neurokinin 1 receptor (NK1R) has been shown to decrease the reinforcing properties of opioids, but it is unknown whether pharmacological NK1R blockade has the same effect. Here, we examined the effect of L822429, a rat-specific NK1R antagonist, on the reinforcing properties of heroin in rats on short (1 h: ShA) or long (12 h: LgA) access to intravenous heroin selfadministration. ShA produces heroin self-administration rates that are stable over time, whereas LgA leads to an escalation of heroin intake thought to model important dependence-related aspects of addiction. L822429 reduced heroin self-administration and the motivation to consume heroin, measured using a progressive-ratio schedule, in both ShA and LgA rats. L822429 also decreased anxietylike behavior in both groups, measured on the elevated plus maze, but did not affect mechanical hypersensitivity observed in LgA rats. Expression of TacR1 (the gene encoding NK1R) was decreased in reward-and stress-related brain areas both in ShA and LgA rats compared with heroin-naïve rats, but did not differ between the two heroin-experienced groups. In contrast, passive exposure to heroin produced increases in TacR1 expression in the prefrontal cortex and nucleus accumbens. Taken together, these results show that pharmacological NK1R blockade attenuates heroin reinforcement. The observation that animals with ShA and LgA to heroin were similarly affected by L822429 indicates that the SP/NK1R system is not specifically involved in neuroadaptations that underlie escalation resulting from LgA self-administration. Instead, the NK1R antagonist appears to attenuate acute, positively reinforcing properties of heroin and may be useful as an adjunct to relapse prevention in detoxified opioid-dependent subjects.

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Section: Elevated Plus Mazementioning

confidence: 99%

The NK1 Receptor Antagonist L822429 Reduces Heroin Reinforcement

Barbier

Vendruscolo

Schlosburg

et al. 2012

Neuropsychopharmacol

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“…The increased amount of time spent in the center of the cage may represent an anxiolytic effect of this TMX treatment. Since rodents typically locate at the periphery of a chamber, movement and positioning to the center of the cage have been interpreted as indicating decreased anxiety [44, 45, 46]. …”

Section: Discussionmentioning

confidence: 99%

Dose-Response Effects of Estrogen and Tamoxifen upon Methamphetamine-Induced Behavioral Responses and Neurotoxicity of the Nigrostriatal Dopaminergic System in Female Mice

Mickley¹,

Dluzen²

2004

Neuroendocrinology

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In the present experiment we evaluated the dose-response effects of estrogen (estradiol benzoate; EB) and tamoxifen (TMX) in modulating the acute behavioral and chronic effects of methamphetamine (MA) upon the nigrostriatal dopaminergic (NSDA) system in ovariectomized (OVX) mice. EB over a range of doses from 1–40 µg resulted in a neuroprotective effect upon the NSDA system as defined by both a preservation of striatal dopamine (DA) concentrations and a decrease in DOPAC/DA ratios. Interestingly, the neuroprotective effect of the 1-µg EB dose occurred in the absence of any statistically significant effect upon the bioassay parameter of uterine weight. With the exception of an increase in stereotypy time as a response to the 40-µg dose, EB at any of the doses tested failed to alter any acute behavioral responses evoked by MA. In response to TMX, a statistically significant NSDA neuroprotectant response was obtained for DOPAC/DA ratios, but not DA concentrations, to doses ranging from 12.5 to 500 µg. No statistically significant effects upon uterine weights were obtained for any of the doses of TMX tested. Behaviorally, TMX at 500 µg had the effect of increasing the amount of time spent in the center of the cage. Taken together these results demonstrate: (1) EB and TMX at relatively low doses can exert a neuroprotective effect against MA; (2) these neuroprotective effects of EB and TMX can occur in the absence of an effect upon the bioassay parameter – uterine weights; (3) the parameter of DOPAC/DA ratio may indicate a more sensitive index of NSDA neuroprotection, and (4) modulatory effects of EB and TMX upon acute behavioral responses of the NSDA system to MA can be distinguished from their neuroprotective actions.

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“…The quinoline ring occurs in various natural products and represents a key motif in medicinal chemistry [9][10][11][12], and its derivatives, quinoline-4-carboxylic acids, are a group of compounds associated with different biological activities, such asantiviral [13], anti-inflammatory [14], antimicrobial [15], anti-atherothrombosis [16], antiemetic [17], anxiolytic [18], antimalarial and antileishmanial [19]. Although quinoline-4-carboxylic acid derivatives exhibit various bioactivities, the research of new quinoline-4-carboxylic acid-based antibacterial drugs has developed slowly.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Antibacterial Evaluation of Some New 2-Phenyl-quinoline-4-carboxylic Acid Derivatives

et al. 2016

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A series of new 2-phenyl-quinoline-4-carboxylic acid derivatives was synthesized starting from aniline, 2-nitrobenzaldehyde, pyruvic acid followed by Doebner reaction, amidation, reduction, acylation and amination. All of the newly-synthesized compounds were characterized by 1 H-NMR, 13 C-NMR and HRMS. The antibacterial activities of these compounds against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis), as well as one strain of methicillin-resistant Staphylococcus aureus (MRSA) bacteria were evaluated by the agar diffusion method (zone of inhibition) and a broth dilution method (minimum inhibitory concentration (MIC)), and their structure-activity relationships were obtained and discussed. The results revealed that some compounds displayed good antibacterial activity against Staphylococcus aureus, and Compounds 5a 4 and 5a 7 showed the best inhibition with an MIC value of 64 µg/mL against Staphylococcus aureus and with an MIC value of 128 µg/mL against Escherichia coli, respectively. The results of the MTT assay illustrated the low cytotoxicity of Compound 5a 4 .

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Evaluation of the anxiolytic-like effect of NKP608, a NK1-receptor antagonist, in two rat strains that differ in anxiety-related behaviors

Abstract: These findings indicate that the anxiety-related effects of NKP608 are strain-, sex- and test-dependent. Moreover, the present data confirm and extend the therapeutic potential of NK1 receptor antagonists for the treatment of anxiety.

Cited by 45 publications

References 43 publications

The NK1 Receptor Antagonist L822429 Reduces Heroin Reinforcement

The NK1 Receptor Antagonist L822429 Reduces Heroin Reinforcement

Dose-Response Effects of Estrogen and Tamoxifen upon Methamphetamine-Induced Behavioral Responses and Neurotoxicity of the Nigrostriatal Dopaminergic System in Female Mice

Design, Synthesis and Antibacterial Evaluation of Some New 2-Phenyl-quinoline-4-carboxylic Acid Derivatives

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