Modification of behavioral responses to methamphetamine evoked by the stimulant's metabolite p-hydroxynorephedrine in rats.
The central effect of p-hydroxynorephedrine (OH-NE), one of the p-hydroxylated metabolites of methamphetamine (MAP) and amphetamine (AMP), was investigated in rats. Locomotion and stereotypy were examined after SC injections of 0.5-5 mg/kg of MAP or 0.02-0.5 mg/kg of apomorphine (APO) in animals treated with either saline or 5-50 mg/kg of OH-NE IP 20 hr before behavioral assessment. The locomotor stimulating effect of both 0.5-2 mg/kg of MAP and 0.2 mg/kg of APO was enhanced by 5 mg/kg of OH-NE. On the other hand, 30 mg/kg of OH-NE severely suppressed the stimulating effect of MAP but had no influence on that induced by 0.2 mg/kg of APO. The stereotypy induced by 5 mg/kg of MAP or 0.5 mg/kg of APO was enhanced and prolonged in the OH-NE-treated rats. Subsequently, examinations were performed to determine whether OH-NE had any effect on the dopaminergic mechanism. Hypomotility induced by 0.02 mg/kg of APO was alleviated by 5 mg/kg of OH-NE, but was aggravated by 30 mg/kg. These results suggest that OH-NE administered prior to SC injections of MAP or APO influences their behavioral effects via the dopaminergic mechanism. The possibility that other neural mechanisms may be involved in this OH-NE-induced behavioral modification is also discussed.
Shimosato
K
K
Department of Legal Medicine, Kawasaki Medical School, Okayama, Japan.
Watanabe
S
S
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D010665:Phenylpropanolamine / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects; D010137:p-Hydroxynorephedrine / Q000494:pharmacology*
D010665:Phenylpropanolamine; D008694:Methamphetamine; D010137:p-Hydroxynorephedrine; D001058:Apomorphine