Methylphenidate (MPD), a psychostimulant, is a prescription medicine for treating attention deficit hyperactivity disorder (ADHD). Previously we have shown that moderate doses of MPD enhanced learning and memory while higher doses impaired it. To understand neurochemical mechanisms and receptors involved in memory enhancing and impairing effects of MPD, the present study concerns the effects of these doses of MPD on serotonin, 5-HT1A, GABA, and NMDA receptor mRNA expression in the prefrontal cortex (PFC). We found that low doses (2.5 mg/kg) of MPD improved performance in the water-maze test but higher doses (5 mg/kg) impaired memory retention. Animals showing improved performance had high 5-HT metabolism in the PFC while these levels were not affected in the group treated with higher MPD doses and exhibiting impaired memory. There was downregulation of 5-HT1A receptors in the PFC of rats treated with higher dose MPD, which didn't occur in low dose of MPD treated animals. Further, a decrease in GABAreceptor mRNA expression occurred in low doses of MPD treated animals and GluN2A expression was reduced in higher doses of MPD treated animals. The findings suggest that memory enhancing doses of MPD increase 5-HT and reduce GABA receptor mRNA expression in the PFC to release excitatory glutamate neurons from the inhibitory influence of GABA. Conversely, higher dose of MPD downregulates 5-HT1A receptor mRNA expression to enhance inhibitory GABA influence on glutamate neurons and impair cognitive performance. The findings show an important role of 5-HT1A heteroreceptors in the PFC for improving therapeutic use of MPD and developing novel cognitive enhancers.
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http://dx.doi.org/10.1016/j.biochi.2021.08.009 | DOI Listing |
Parasit Vectors
December 2024
Boehringer Ingelheim Vetmedica GmbH, Binger Str. 173, 55216, Ingelheim am Rhein, Germany.
Background: Two studies were conducted assessing the efficacy of NexGard® PLUS (NP) in preventing heartworm disease. Study 1 evaluated the efficacy of six monthly doses of NP or Simparica Trio® (ST) against a macrocyclic lactone-resistant isolate of heartworm, Dirofilaria immitis, and study 2 evaluated the efficacy of a single dose of NP against a susceptible isolate.
Methods: In two studies, dogs that were negative for heartworms by antigen test and modified Knott's test were used.
J Am Med Dir Assoc
October 2024
Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium; Department of Public Health and Primary Care, Gerontology and Geriatrics, KU Leuven, Leuven, Belgium.
Objectives: Chronic antipsychotic use among nursing home (NH) residents carries risks with uncertain benefits. Despite guidelines recommending restricted use, these agents remain widely prescribed. This study investigates chronic antipsychotic use in Belgian NHs.
View Article and Find Full Text PDFInt J Mol Sci
July 2024
Physiology Department Medical School, National Autonomous University of Mexico, Ciudad de México 04510, Mexico.
Methylphenidate (MPD) remains a cornerstone pharmacological intervention for managing ADHD, yet its increasing usage among ordinary youth and adults outside clinical contexts necessitates a thorough investigation into its developmental effects. This study seeks to simultaneously investigate the behavioral and neuronal changes within the dorsal raphe (DR) nucleus, a center of serotonergic neurons in the mammalian brain, before and after the administration of varying doses of acute and chronic MPD in freely behaving young and adult rats implanted with DR recording electrodes. Wireless neuronal and behavioral recording systems were used over 10 consecutive experimental days.
View Article and Find Full Text PDFJ Pers Med
June 2024
Faculty of Pharmacy, Université de Montréal, Montreal, QC H3T 1J4, Canada.
Commun Med (Lond)
May 2024
Genentech; 1 DNA Way, South San Francisco, CA, 94080, USA.
Background: Proteolysis-targeting chimeras (PROTACs) are being developed for therapeutic use. However, they have poor pharmacokinetic profiles and their tissue distribution kinetics are not known.
Methods: A typical von Hippel-Lindau tumor suppressor (VHL)-PROTAC C-A947 (BRM degrader)-was synthesized and its tissue distribution kinetics was studied by quantitative whole-body autoradiography (QWBA) and tissue excision in rats following IV dosing.
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