Biomaterial Database

Effects of glutamate-related drugs on anxiety and compulsive behavior in rats with obsessive-compulsive disorder. 2020

Yuhua Zhan, and Jing Xia, and Xumei Wang

Department of Psychiatry, Shengjing Hospital of China Medical University, Shenyang, China.

Objective: Altered glutamatergic neurotransmission has been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). We examined the effects and potential mechanism of glutamate-related drugs on compulsive behavior in quinpirole (QNP)-sensitized rats, to deepen our understanding of the link between OCD and glutamate.Method: This study systematically compared the effects of the partial NMDA agonist D-Cycloserine and the NMDA antagonist NVP-AAMO77, Ro25-6981 on compulsive behavior using the elevated zero maze, open field, and marble burying tests in QNP-induced OCD model.Results: The competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists NVP-AAMO77 (5 mg/kg) and Ro25-6981 (5 mg/kg) significantly inhibited anxiety-like and compulsive behavior in rats. And D-Cycloserine at all doses showed significant suppression on anxiety-like and marble-burying behavior. Glutamic acid (Glu) levels, reflecting changes in the glutamatergic neurotransmission, were significantly decreased in rat hippocampus of the NVP-AAMO77 and D-Cycloserine-treated group compared to the saline-treated group. The levels of other amino acids were unaffected. Moreover, NVP-AAMO77 significantly decreased the expression of the subunit NR2A of the NMDAR, and Ro25-6981 suppressed the level of the subunit NR2B of the NMDAR, while D-Cycloserine decreased both the subunit NR2A and NR2B of the NMDAR.Conclusion: Collectively, these findings suggest a functional role of NMDARs in anxiety and compulsive behaviors, with NMDARs inhibition promoting anxiolytic-like and anti-compulsive responses. These findings suggest that D-cycloserine, NVP-AAMO77, and Ro25-6981 could be useful drugs for the treatment of OCD, which may be due to the suppression of NR2A- or NR2B- containing NMDAR.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009435	Synaptic Transmission	The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.	Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009771	Obsessive-Compulsive Disorder	An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension.	Anankastic Personality,Neurosis, Obsessive-Compulsive,Anankastic Personalities,Disorder, Obsessive-Compulsive,Disorders, Obsessive-Compulsive,Neuroses, Obsessive-Compulsive,Neurosis, Obsessive Compulsive,Obsessive Compulsive Disorder,Obsessive-Compulsive Disorders,Obsessive-Compulsive Neuroses,Obsessive-Compulsive Neurosis,Personalities, Anankastic,Personality, Anankastic
D003192	Compulsive Behavior	The behavior of performing an act persistently and repetitively without it leading to reward or pleasure. The act is usually a small, circumscribed behavior, almost ritualistic, yet not pathologically disturbing. Examples of compulsive behavior include twirling of hair, checking something constantly, not wanting pennies in change, straightening tilted pictures, etc.	Behavior, Compulsive,Behaviors, Compulsive,Compulsive Behaviors
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001007	Anxiety	Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS.	Angst,Anxiousness,Hypervigilance,Nervousness,Social Anxiety,Anxieties, Social,Anxiety, Social,Social Anxieties
D001522	Behavior, Animal	The observable response an animal makes to any situation.	Autotomy Animal,Animal Behavior,Animal Behaviors
D016194	Receptors, N-Methyl-D-Aspartate	A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.	N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D017207	Rats, Sprague-Dawley	A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.	Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats