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Stereoselective effects of methcathinone on intracranial self‐stimulation in rats
Author(s) -
Bonano Julie Suyama,
Banks Matthew L,
Glen Richard A,
Negus S Stevens
Publication year - 2013
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.27.1_supplement.1098.2
Subject(s) - methamphetamine , stimulation , pharmacology , medial forebrain bundle , mephedrone , chemistry , brain stimulation reward , drugs of abuse , psychology , medicine , neuroscience , central nervous system , nucleus accumbens , striatum , drug , dopamine
Methcathinone (MCAT), the β‐keto analog of methamphetamine, is a potent central nervous system stimulant and parent compound to emerging drugs of abuse such as methylone, mephedrone, and MDPV ( bath salts ). Intracranial self‐stimulation (ICSS) is one type of procedure that has been used to assess abuse liability of stimulants and other classes of abused drugs. This study compared the potency, time course, and profile of effects produced by intraperitoneal administration of the (−) and (+) isomers of MCAT on ICSS in rats. Male Sprague Dawley rats were equipped with electrodes targeting the medial forebrain bundle, and responding during daily behavioral sessions was maintained by a range of 10 brain stimulation frequencies (56–158 Hz in 0.05 log steps). After saline treatment, brain stimulation maintained a frequency‐dependent increase in ICSS rates. Both (−)‐ and (+)‐MCAT produced a dose‐dependent and abuse‐related facilitation of ICSS that peaked after 10 min and was no longer evident after 300 min. (−)‐MCAT was approximately 3‐fold more potent than the less active (+) isomer. The stereoselectivity of MCAT effects on ICSS agrees with its stereoselectivity in producing other abuse‐related behavioral effects. These studies provide a foundation for future structure‐activity studies of abuse‐related effects produced by MCAT derivatives in this ICSS assay in rats. Funded by NIH grant R01 DA033930.