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Tytuł pozycji:

Repeated administration of methylphenidate produces reinforcement and downregulates 5-HT-1A receptor expression in the nucleus accumbens.

Tytuł:
Repeated administration of methylphenidate produces reinforcement and downregulates 5-HT-1A receptor expression in the nucleus accumbens.
Autorzy:
Salman T; Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: .
Nawaz S; Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Waraich RS; Pathobiochemistry and Molecular Physiology Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Haleem DJ; Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: .
Źródło:
Life sciences [Life Sci] 2019 Feb 01; Vol. 218, pp. 139-146. Date of Electronic Publication: 2018 Dec 27.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
MeSH Terms:
Central Nervous System Stimulants/*pharmacology
Maze Learning/*drug effects
Memory/*drug effects
Methylphenidate/*pharmacology
Nucleus Accumbens/*metabolism
Prefrontal Cortex/*metabolism
Receptor, Serotonin, 5-HT1A/*metabolism
Animals ; Central Nervous System Stimulants/administration & dosage ; Down-Regulation ; Male ; Methylphenidate/administration & dosage ; Nucleus Accumbens/drug effects ; Prefrontal Cortex/drug effects ; Rats ; Receptor, Serotonin, 5-HT1A/chemistry ; Receptor, Serotonin, 5-HT1A/genetics
Contributed Indexing:
Keywords: Addiction; Cognition; Conditioned place-preference; Methylphenidate; qRT-PCR
Substance Nomenclature:
0 (Central Nervous System Stimulants)
112692-38-3 (Receptor, Serotonin, 5-HT1A)
207ZZ9QZ49 (Methylphenidate)
Entry Date(s):
Date Created: 20181231 Date Completed: 20190301 Latest Revision: 20190301
Update Code:
20240105
DOI:
10.1016/j.lfs.2018.12.046
PMID:
30594665
Czasopismo naukowe
Aims: Methylphenidate (MPD) widely prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), is a psychostimulant and can produce addiction in patients treated with it. In view of growing increase in the use of drug by general population as a cognitive enhancer, the present study is designed to investigate reinforcing and cognition enhancing effects of MPD in rats. Associated changes in serotonin-1A receptor expression are investigated as a potential molecular mechanism involved.
Methods: Learning acquisition and memory retention in Morris water-maze test were used to assess cognitive effects of MPD. Reinforcing effects were evaluated in conditioned place-preference (CPP) paradigm. The expression of 5-hydroxytryptamine (5-HT; serotonin)-1A receptor in the nucleus accumbens and prefrontal cortex of repeated MPD treated animals was determined by qRT-PCR.
Findings: Lower doses (0.5 and 2.5 mg/kg) of MPD enhanced learning acquisition and memory retention but higher doses (5 mg/kg) impaired these. The drug administered repeatedly at a dose of 2.5 mg/kg was reinforcing in CPP test, but sensitization like effects of this dose were only transient. These animals tested in water-maze test exhibited improved memory retention but no effect occurred on learning acquisition. The expression of 5-HT-1A receptor was markedly attenuated in the nucleus accumbens; attenuation in the prefrontal cortex was not significant.
Significance: The findings suggest that clinically relevant doses of MPD can produce drug addiction, but effects of the drug on memory retention are retained. A downregulation of 5-HT-1A receptor in the nucleus accumbens seems important in the reinforcing effects of MPD.
(Copyright © 2019 Elsevier Inc. All rights reserved.)

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