The effects of the epileptogenic agent, picrotoxin, on both the cardiovascular responses and the dopamine (DA) release in the amygdala were studied in anesthetized rats. In vivo voltammetry was used to measure change in extracellular concentrations of DA and its metabolites in the amygdala. Intravenous administration of picrotoxin produced hypertension, increased amygdaloid DA release and behavioral syndromes (such as increased masticatory movements, salivation, and forepaw tremors). Direct administration of picrotoxin into the amygdala also induced the same effects. The picrotoxin-induced effects were suppressed by activation of gamma-aminobutyric acid (GABA) receptors with diazepam or depleting brain DA with 6-hydroxydopamine. Blockade of central DA receptors with haloperidol also attenuated the picrotoxin-induced hypertension. These results indicate that picrotoxin affects interactions between GABA neurons and DA system in rat brain to induce hypertension during an epileptic attack.
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http://dx.doi.org/10.1016/s0304-3940(96)13155-4 | DOI Listing |
Food Chem Toxicol
March 2025
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong 264003, China. Electronic address:
Based on the concept of continuous dopaminergic stimulation (CDS), Rotigotine Behenate extended-release microspheres for injection (RBEM) are currently under development. To support human clinical trials of RBEM, a 20-week repeat-dose toxicity study was conducted. SD rats intramuscularly received RBEM (60, 180, and 540 mg/kg) once every 4 weeks for 5 repeated doses followed by a 12-week recovery period, no clear sex difference was noted in the plasma exposure of rotigotine in rats, and the exposure generally increased in a dose-proportional manner.
View Article and Find Full Text PDFToxicol Sci
March 2025
Cerevel Therapeutics, LLC, Cambridge, MA.
Dopamine agonists (DAs) are approved for the treatment of hypodopaminergic pathologies, including Parkinson's disease, restless legs syndrome, and periodic limb movement disorder. During drug development, drugs acting on dopaminergic receptors are often associated with a rat-specific endocrine tumor response, including changes in fertility, which are ascribed to DA-induced suppression of pituitary prolactin release. Although these effects are not observed in or relevant to humans, given species differences in the effects of prolactin on reproductive organs, modeling DA-mediated changes in prolactin and the reproductive system remains important for preclinical drug development.
View Article and Find Full Text PDFPharmacol Rep
March 2025
Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland.
Background: A number of rodent studies have investigated the effects of alcohol (ethanol) administration on the catecholaminergic neurotransmitters, norepinephrine (NE) and dopamine (DA). These studies suggest that presentation of alcohol to mice or rats can alter brain levels of NE and DA, in various subregions. Other studies have presented the hypothesis that there may be an unidentified pathway in rodents, and other organisms, that actually transforms ethanol to NE or DA.
View Article and Find Full Text PDFColloids Surf B Biointerfaces
March 2025
State Key Laboratory of Swine and Poultry Breeding Industry, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China. Electronic address:
Treating bacterium-infected diabetic wounds remains a major medical challenge. Antimicrobial activity, remodeling of oxidative stress-heavy and angiogenesis-impaired microenvironments are critical factors for effective wound healing. Hydrogels can function as drug delivery systems that encompass all these capabilities to enhance wound healing.
View Article and Find Full Text PDFBehav Brain Funct
March 2025
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
Background: Major depressive disorder is a significant global cause of disability, particularly among adolescents. The dopamine system and nearby neuroinflammation, crucial for regulating mood and processing rewards, are central to the frontostriatal circuit, which is linked to depression. This study aimed to investigate the effect of post-weaning isolation (PWI) on depression in adolescent mice, with a focus on exploring the involvement of microglia and dopamine D1 receptor (D1R) in the frontostriatal circuit due to their known links with mood disorders.
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