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Effects of m‐fluoroamphetamine and fenfluramine on intracranial self‐stimulation (ICSS) in rats
Author(s) -
Bauer Clayton Thomas,
Banks Matthew L,
Blough Bruce E,
Negus Sidney S.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.795.21
Monoamine releasers such as amphetamine are used clinically for various indications and are also under consideration as agonist medications for treatment of cocaine addiction. Abuse liability of monoamine releasers may be influenced by their relative ability to release dopamine vs. serotonin, with increasing abuse liability associated with increasing selectivity to release dopamine. This study compared effects of the dopamine‐selective releaser m‐fluoroamphetamine (m‐FA) and the serotonin‐selective releaser fenfluramine (Fen) in an assay of intracranial self‐stimulation (ICSS) in male Sprague‐Dawley rats. Electrical stimulation (58–156 Hz) of the medial forebrain bundle maintained a frequency‐dependent increase in reinforcement rates. m‐FA (0.1–1.0 mg/kg IP) produced a dose‐dependent facilitation of ICSS, manifested as significant leftward shifts in the frequency‐rate curve. This abuse‐related effect peaked after 10 min and was no longer apparent after 300 min. In contrast, Fen (0.32–3.2 mg/kg IP) produced a longer‐acting depression of ICSS. These findings demonstrate opposing effects of dopamine‐ and serotonin‐selective releasers on ICSS. Supported by NIH grant R01 26946.