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Effects of monoaminergic drugs in monkeys discriminating a low dose of methamphetamine
Author(s) -
Bergman Jack,
Zakarian Ani,
Paronis Carol A
Publication year - 2006
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.20.4.a680-b
Subject(s) - methamphetamine , pharmacology , monoaminergic , chemistry , desipramine , serotonergic , dopaminergic , agonist , dopamine , probenecid , serotonin , medicine , antidepressant , hippocampus , receptor , biochemistry
The present studies were conducted to evaluate the role of dopaminergic (DA) and non‐DA actions in the discriminative‐stimulus (Sd) effects of a relatively low i.m. dose of methamphetamine (MA) in monkeys. Subjects (n=4) initially were trained under a 10‐response fixed‐ratio schedule to press one of two levers after i.m. injection of 0.056 mg/kg MA—the lowest i.m. training dose that reliably maintained drug discrimination performance. When responding was stable, cumulative i.m. dosing procedures were used to study substitution by direct and indirectly‐acting monoaminergic agonists for MA. Test drugs included D1 and D2 full agonists [SKF 82958 (0.03–1.0 mg/kg) and (+)−PHNO (0.0003–0.01 mg/kg)], D1 and D2 partial agonists [SKF 83959 (0.03–3.0 mg/kg) and terguride (0.01–0.1 mg/kg)], and the reuptake inhibitors GBR 12909 (DA‐selective; 0.1–3.0 mg/kg), citalopram and fluoxetine (serotonin‐selective; 0.1–10.0 mg/kg), and desipramine and tomoxetine (norepinephrine‐selective; 0.1–10.0 mg/kg). Results show that only the D1 and D2 full agonists and the DA‐selective uptake inhibitor consistently engendered dose‐related increases in responding on the MA‐associated lever, with a maximum of 75–100% substitution following 0.56 mg/kg SKF 82958, 0.003 mg/kg (+)−PHNO, and 1.8 mg/kg GBR 12909. The highest degree of substitution among the remaining drugs was produced by 0.032 mg/kg terguride, which fully substituted for the training dose of MA in only two subjects. In a final set of experiments, pretreatment with 3.0 mg/kg SKF 83959 produced a 10‐fold rightward shift in the MA dose‐effect function, indicative of surmountable antagonism. These findings support the view that DA mechanisms play a pivotal role in the Sd effects of moderate MA doses. (supported by NIH/NIDA DA03774, DA10566)