Persistent supersensitivity of sigma receptors develops during repeated methamphetamine treatment.
Functional changes in sigma receptors were examined after behavioral sensitization induced by repeated methamphetamine treatment. Rats received either saline or 4 mg/kg methamphetamine for 14 days. (+)3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP), a sigma receptor agonist, was given as challenge after various periods of abstinence. (+)-3-PPP at doses greater than 6 mg/kg stimulated several forms of behavior in naive rats. (+)-3-PPP at 12 and 24 mg/kg produced more frequent rearing and more intense stereotyped sniffing and repetitive head movements in rats previously sensitized with methamphetamine than in saline-pretreated rats. The augmented response to (+)-3-PPP in methamphetamine-treated rats was maintained for at least one month. The augmented response to (+)-3-PPP was reversed by the combined administration of 100 mg/kg (+/-)-sulpiride, a D2 dopamine receptor antagonist, and 30 mg/kg BMY 14802, a sigma receptor antagonist. These results suggest that repeated methamphetamine treatment induces persistent supersensitivity in sigma receptors and that it may subsequently activate the dopamine system.
Department of Neuropsychiatry, Okayama University Medical School, Japan.
H
H
Ujike
K
K
Okumura
Y
Y
Zushi
K
K
Akiyama
S
S
Otsuki
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017480:Receptors, sigma
D015259:Dopamine Agents; D010880:Piperidines; D011957:Receptors, Opioid; D017480:Receptors, sigma; D008694:Methamphetamine; C026539:preclamol