Search results for "Excitatory Amino Acid Antagonists"
showing 10 items of 55 documents
A "double hit" murine model for schizophrenia shows alterations in the structure and neurochemistry of the medial prefrontal cortex and the hippocamp…
2013
Both alterations in neurodevelopment and aversive experiences during childhood and adolescence seem important risk factors for schizophrenia. Animal models reproducing these alterations mimic some of the symptoms, constituting a valid approach to study the etiopathology of this disorder. Among these models, the perinatal injection of N-methyl-d-aspartate receptor antagonists and the postweaning social isolation rearing are among the most widely used. Our aim is to combine them in a "double hit" model, which should produce a wider spectrum of alterations. Lister Hooded rats have been subjected to a single injection of MK-801 at postnatal day 7 and socially isolated from postweaning to adulth…
Neuroprotection of S(+) ketamine isomer in global forebrain ischemia
2001
The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine can block the action of excitotoxic amino acids in the central nervous system. S(+) ketamine has a 2-3 times higher anesthetic potency compared with the ketamine-racemate and also shows a higher neuroprotective efficacy in vitro. To determine the neuroprotective activity of S(+) ketamine compared with its R(-) stereoisomer in vivo, we examined the functional and neurohistological outcome in rats treated 15 min after global forebrain ischemia with S(+) ketamine in different dosages compared with R(-) ketamine. Influence of the treatment on regional cerebral blood flow (rCBF) and cortical oxygen saturation (HbO2) was…
Effect of memantine and CNQX in the acquisition, expression and reinstatement of cocaine-induced conditioned place preference
2006
The present study evaluates the effect of memantine, a non-competitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist and CNQX, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist on the rewarding effects of cocaine in mice, using the conditioned place preference (CPP) paradigm. Cocaine-induced CPP was studied pairing this drug with different memantine or CNQX doses during either the acquisition or the expression phase of the procedure. Once CPP was established, and the preference extinguished, reinstatement was induced by a priming dose of cocaine. Both antagonists, which in themselves do not present motivational actions on the preferen…
NMDA glutamate but not dopamine antagonists blocks drug-induced reinstatement of morphine place preference.
2004
The effects of dopaminergic and glutamatergic antagonists on the drug-induced reinstatement of a previously extinguished morphine conditioned place preference (CPP) in mice were evaluated. Following extinction of a place preference induced by morphine (40 mg/kg), a non-contingent injection of the dopaminergic antagonists SCH 23390 (0.125, 0.5 mg/kg), raclopride (0.3, 1.2 mg/kg), haloperidol (0.1, 0.2 mg/kg) and the dopamine (DA) release inhibitor CGS 10746B (1, 10 mg/kg) or glutamatergic NMDA antagonists memantine (10, 20, 40 mg/kg) and MK-801 (0.1, 0.2, 0.3 mg/kg) alone or with 10 mg/kg morphine was given. Neither the dopaminergic nor the glutamatergic antagonists alone reinstated the plac…
Synthesis, resolution, stereochemistry, and molecular modeling of (R)- and (S)-2-acetyl-1-(4’-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinol…
2007
Abstract Recently we identified ( R , S )-2-acetyl-1-(4′-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ( 6 ) as a potent non-competitive AMPA receptor antagonist able to prevent epileptic seizures. We report here the optimized synthesis of compound 6 , its resolution by chiral preparative HPLC, and the absolute configuration of ( R )-enantiomer established by X-ray diffractometry. The biological tests of the single enantiomers revealed that higher anticonvulsant and antagonistic effects reside in ( R )-enantiomer as also suggested by molecular modeling studies.
Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA.
2015
Some 3,4-methylenedioxymethamphetamine (MDMA) users become dependent as a result of chronic consumption. A greater understanding of the neurobiological basis of the rewarding effects of MDMA could contribute to developing effective pharmacotherapies for MDMA-related problems. The present study evaluated the role of N-methyl-D-aspartate (NMDA) glutamate receptors (NMDARs) in the acquisition and reinstatement of conditioned place preference (CPP) induced by MDMA. Adolescent male mice were conditioned with 1 or 10 mg/kg MDMA and pretreated with 5 or 10 mg/kg of the NMDAR antagonist memantine during acquisition of conditioning (experiment 1), or before a reinstatement test (experiment 2). In ad…
Memantine blocks sensitization to the rewarding effects of morphine
2009
Knowledge regarding the specific brain changes and neural plasticity processes produced by repeated drug exposure may be used to advance the understanding of the neurobiology of addiction in order to design appropriate medications. In the present study, the influence of N-methyl-d-aspartate (NMDA) glutamatergic receptors on sensitization to the motor and rewarding effects of morphine was evaluated. The effects of pre-exposure to saline or 20 mg/kg morphine plus the NMDA receptor antagonist memantine (10 or 20 mg/kg) on motor activity and place conditioning induced by a low dose of morphine (2 mg/kg) were assessed. The dose of 2 mg/kg of morphine was ineffective in mice pre-exposed to saline…
Memantine presents different effects from MK-801 in motivational and physical signs of morphine withdrawal
2003
Adaptive changes in neural systems due to chronic opiate exposure are related to the neural plasticity phenomenon, NMDA receptors being implicated in these processes, e.g. tolerance, dependence or withdrawal. In this work, we investigated the effect of two non-competitive NMDA antagonists, memantine and MK-801, in motivational (Conditioned Place Aversion paradigm, CPA) and physical aspects of morphine withdrawal. After the induction of morphine dependence, animals in which the CPA was studied, received memantine (5 and 10 mg/kg) or MK-801 (0.3-0.006 mg/kg) either during the acquisition (conditioning) or expression (test) phase of this procedure. Both drugs were capable of inhibiting conditi…
Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area μ Opioid Receptors
2015
Pain management in opioid abusers engenders ethical and practical difficulties for clinicians, often resulting in pain mismanagement. Although chronic opioid administration may alter pain states, the presence of pain itself may alter the propensity to self-administer opioids, and previous history of drug abuse comorbid with chronic pain promotes higher rates of opioid misuse. Here, we tested the hypothesis that inflammatory pain leads to increased heroin self-administration resulting from altered mu opioid receptor (MOR) regulation of mesolimbic dopamine (DA) transmission. To this end, the complete Freund's adjuvant (CFA) model of inflammation was used to assess the neurochemical and functi…
Ineffectiveness of dextromethorphan in cancer pain
1998
Experimental studies have indicated that N-methyl-D-aspartate (NMDA) receptor antagonists may be effective analgesics in a wide variety of chronic pain states. The mechanism is presumed to be related to decreased firing of dorsal horn neurons after constant repeated C-fiber stimulation. Dextromethorphan (DM), a potent NMDA antagonist with a good safety profile, may be a promising agent for the treatment of persistent pain. An open-label randomized trial was designed to examine the effects of combining DM with NSAIDs, dextropropoxyphene, or morphine in cancer patients with pain. Patients who required a change in the step of the World Health Organization's (WHO) analgesic ladder because of a …