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Antagonism of the Rate‐Decreasing Effects of Abused Psychostimulants and Bath Salt Component Mephedrone in Rats
Author(s) -
Saber Iman A.,
Walker Ellen A.
Publication year - 2016
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.30.1_supplement.1184.2
Subject(s) - methamphetamine , mephedrone , pharmacology , mdma , amphetamine , cathinone , stimulant , chemistry , sch 23390 , dextroamphetamine , dopamine , antagonist , antagonism , dopaminergic , drug , medicine , endocrinology , receptor , biochemistry
To compare the potencies to decrease ongoing behavior among the monoamine alkaloid derivatives of the amphetamine class and the synthetic cathinone mephedrone, 12 food‐restricted male Sprague‐Dawley rats were trained to respond on a fixed ratio 5 schedule of reinforcement for banana‐flavored sucrose pellets. Dose‐response curves for the behavioral effects of d ‐amphetamine, methamphetamine, 3,4‐methylenedioxy‐methamphetamine (MDMA), and mephedrone were determined in a multiple‐trial, cumulative dosing procedure. In addition, the rate‐decreasing effects of these psychomotor stimulants were examined in combination with dopamine (DA) antagonists to assess the role of subtypes of DA receptors in the rate‐decreasing effects of the psychostimulants. When multiple doses of DA 1 antagonist SCH23390 were combined with a moderate dose of methamphetamine (1.0 mg/kg), an antagonism was observed. However, SCH23390 also appeared to have dose‐dependent, rate‐decreasing properties of its own potentially explaining the observed combined rate‐decreasing effects with the lower and higher doses of the stimulants. The DA 2/3 antagonist, sulpiride, slightly attenuated the effects of low and moderate doses of both d‐amphetamine and methamphetamine. When combined with MDMA and mephedrone, attenuation occurred at low and moderate doses, respectfully. These results support previous work demonstrating the similarities and differences between these commonly abused CNS drugs in respects to dopamine activation. Furthermore, this dopaminergic comparison may apply to novel substituted amphetamines and provide insight for mechanisms underlying the pharmacological effects of novel cathinone derivatives such as mephedrone.