Investigation of diazepam efficacy on anxiety-like behavior in hemiparkinsonian rats. 2016

Katherine A O'Connor, and Paul J Feustel, and Adolfo Ramirez-Zamora, and Eric Molho, and Julie G Pilitsis, and Damian S Shin
Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Ave, Albany, NY 12208, USA.

There is growing recognition that anxiety disorders have a greater impact on quality of life in Parkinson's disease than motor symptoms. Yet, little is known about the pathophysiology underlying this non-motor symptom in Parkinson's disease which poses a considerable barrier in developing effective treatment strategies. Here, we administered diazepam to hemiparkinsonian and non-parkinsonian rats and assessed its efficacy in three anxiety behavioral tests. At present, no information about this exists in preclinical research with sparse data in the clinical literature. Moreover, diazepam is an acute anxiolytic which makes this drug a suitable research tool to unmask differences in anxiety-like behavior. Using the unilateral, medial forebrain bundle 6-hydroxydopamine rat model of Parkinson's disease, we noted that hemiparkinsonian rats had more baseline anxiety-like behavior with 60% of them exhibiting high anxiety (HA) behavior in the elevated plus maze. In contrast, 41% of sham-lesioned rats and 8% of naïve rats exhibited HA behavior. Next, we employed the elevated plus maze and noted that diazepam (1.5mg/kg) was anxiolytic in low anxiety (LA) sham-lesioned (p=0.006) and HA sham-lesioned rats (p=0.016). Interestingly, diazepam was anxiolytic for LA hemiparkinsonian rats (p=0.017), but not for HA hemiparkinsonian rats (p=0.174) despite both groups having similar motor impairment and parkinsonian phenotype. Overall, diazepam administration unmasked differences in anxiolytic efficacy between HA hemiparkinsonian rats, LA hemiparkinsonian rats and non-parkinsonian rats. Our data suggests that neuro-circuits involved in anxiety-like behavior may differ within these groups and posits that diazepam may have reduced efficacy in certain individuals with PD anxiety disorders.

UI MeSH Term Description Entries
D007839 Functional Laterality Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot. Ambidexterity,Behavioral Laterality,Handedness,Laterality of Motor Control,Mirror Writing,Laterality, Behavioral,Laterality, Functional,Mirror Writings,Motor Control Laterality,Writing, Mirror,Writings, Mirror
D008297 Male Males
D008474 Medial Forebrain Bundle A complex group of fibers arising from the basal olfactory regions, the periamygdaloid region, and the septal nuclei, and passing to the lateral hypothalamus. Some fibers continue into the tegmentum. Median Forebrain Bundle,Bundle, Medial Forebrain,Bundle, Median Forebrain,Bundles, Medial Forebrain,Bundles, Median Forebrain,Forebrain Bundle, Medial,Forebrain Bundle, Median,Forebrain Bundles, Medial,Forebrain Bundles, Median,Medial Forebrain Bundles,Median Forebrain Bundles
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D003975 Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity. 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
D005106 Exploratory Behavior The tendency to explore or investigate a novel environment. It is considered a motivation not clearly distinguishable from curiosity. Curiosity,Novelty-Seeking Behavior,Behavior, Exploratory,Behavior, Novelty-Seeking,Behaviors, Exploratory,Behaviors, Novelty-Seeking,Curiosities,Exploratory Behaviors,Novelty Seeking Behavior,Novelty-Seeking Behaviors
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
D001008 Anxiety Disorders Persistent and disabling ANXIETY. Anxiety Neuroses,Anxiety States, Neurotic,Neuroses, Anxiety,Anxiety Disorder,Anxiety State, Neurotic,Disorder, Anxiety,Disorders, Anxiety,Neurotic Anxiety State,Neurotic Anxiety States,State, Neurotic Anxiety,States, Neurotic Anxiety
D014151 Anti-Anxiety Agents Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here. Anti-Anxiety Agent,Anti-Anxiety Drug,Anxiolytic,Anxiolytic Agent,Anxiolytic Agents,Tranquilizing Agents, Minor,Anti-Anxiety Drugs,Anti-Anxiety Effect,Anti-Anxiety Effects,Antianxiety Effect,Antianxiety Effects,Anxiolytic Effect,Anxiolytic Effects,Anxiolytics,Tranquillizing Agents, Minor,Agent, Anti-Anxiety,Agent, Anxiolytic,Agents, Anti-Anxiety,Agents, Anxiolytic,Agents, Minor Tranquilizing,Agents, Minor Tranquillizing,Anti Anxiety Agent,Anti Anxiety Agents,Anti Anxiety Drug,Anti Anxiety Drugs,Anti Anxiety Effect,Anti Anxiety Effects,Drug, Anti-Anxiety,Drugs, Anti-Anxiety,Effect, Anti-Anxiety,Effect, Antianxiety,Effect, Anxiolytic,Effects, Anti-Anxiety,Effects, Antianxiety,Effects, Anxiolytic,Minor Tranquilizing Agents,Minor Tranquillizing Agents
D016627 Oxidopamine A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals. 6-Hydroxydopamine,6-OHDA,Oxidopamine Hydrobromide,Oxidopamine Hydrochloride,6 Hydroxydopamine,Hydrobromide, Oxidopamine,Hydrochloride, Oxidopamine

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