Lever pressing of rats was maintained in different chambers during two different sessions each day. At 0900 h, responding was maintained under a two-component multiple schedule in which responses initiated an interval that had to elapse before delivery of food (time delay of 20 s and 40 s). In this schedule, a 'response-pause' sequence preceded reinforcers, and acutely administered diazepam only decreased responding. At 1400 h, responding by the same subjects was maintained under a different two-component multiple schedule, in which individual responses initiated an interval that had to be terminated by another response before delivery of food (DRL 20 s and 40 s). In this second schedule, a 'response-pause-response' sequence preceded reinforcers, and acutely administered diazepam increased responding. After studying the acute behavioral effects of diazepam during each separate 'timing' schedule, animals systematically received 1.7 mg/kg per day diazepam 2-5 min prior to their different schedule components, in order to study the influence of reinforcement contingency on the chronic effects of this drug. Diminution of the initial effects of diazepam during daily drug administration prior to DRL 20 s responding did not extend to DRL 40 s responding or to time-delay responding, and tolerance did not develop at all for time-delay responding. When diazepam was again administered after all the daily schedules for approximately 1 month, and then given before the individual DRL schedules, DRL responding was increased again as it had been prior to chronic drug administration. These results suggest that the behavioral effects of acutely administered diazepam are influenced by different 'timing' requirements, and that the behavioral effects of chronically administered diazepam are influenced by 'timing' requirements and by drug- and chamber-related stimuli.
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http://dx.doi.org/10.1097/00008877-200002000-00005 | DOI Listing |
Synapse
January 2025
Department of Biochemistry & Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh.
Sesamol (SES) and linalool (LIN) are aromatic compounds that have neuroprotective effects. The main purpose of this study is to evaluate the anxiolytic activity of LIN and SES co-treatment on Swiss albino mice and analyze its possible mechanism through in silico study. In this sense, the mice were given the gamma-aminobutyric acid type A receptors (GABA) agonist diazepam (DZP; 3 mg/kg, p.
View Article and Find Full Text PDFNeurotherapeutics
December 2024
Department of Neurology and Neuroscience Brain Institute University of Virginia, School of Medicine, Health Sciences Center, Box 801330, Charlottesville, VA 22908-1330, USA. Electronic address:
Generalized Convulsive status epilepticus (SE) is a neurological emergency because prolonged convulsions can cause respiratory compromise and neuronal injury. Compromised GABA-mediated inhibition is a defining feature of SE, and many current therapies are benzodiazepines, which are allosteric modulators of GABA-A receptors. Many patients with medically refractory epilepsy are at risk for SE.
View Article and Find Full Text PDFBehav Brain Res
December 2024
Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj 8100, Bangladesh; Pharmacy Discipline, Khulna University, Khulna 9208, Bangladesh. Electronic address:
Background: Anxiety disorder is the most common mental illness and a major contributor to impairment. Thus, there is an urgent need to find novel lead compounds to mitigate anxiety. It is widely recognized that the neurobiology of anxiety-related behavior involves GABAergic systems.
View Article and Find Full Text PDFChem Biodivers
December 2024
State University of Acaraú Valley, Chemistry, RODOVIA CE 040, Casa 21 quadra 13, 61760000, Aquiraz, BRAZIL.
This study investigated the anxiolytic, anticonvulsant and memory preservation effects of the flavonoid robinin. The compound, administered at doses of 4, 20 and 40 mg/kg, did not show toxicity after 96 hours of monitoring. In behavioral experiments with zebrafish, robinin did not cause significant changes in motor functions, but it impairs locomotor activity and demonstrates anxiolytic properties, evidenced by the increase in the time spent in the clean zone of the protector.
View Article and Find Full Text PDFEpilepsia
November 2024
Neurelis, Inc., San Diego, California, USA.
Objective: Benzodiazepine rescue medications are established as therapy for acute termination of seizure clusters. A post-hoc analysis of a clinical trial of seizure cluster treatment with diazepam nasal spray found a potential longer-term impact over a year of treatment. In this retrospective analysis, we tested the hypothesis that benzodiazepine-treated seizure clusters are associated with prolonged time to the next seizure cluster compared with untreated seizure clusters in a patient-reported real-world database.
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