title: Pretreatment with nomifensine or nomifensine analogue 4-phenyl-1,2,3,4-tetrahydroisoquinoline augments methamphetamine-induced stereotypical behavior in mice.
abstract: Nomifensine is a dopamine/norepinephrine reuptake inhibitor. Nomifensine and some of its structural analogues produce behavioral effects indicative of indirect dopaminergic agonist properties, such as hyperlocomotion. By contrast, the deaminated and demethylated nomifensine analogue 4-phenyl-1,2,3,4-tetrahydroisoquinoline (PTIQ) is reported to have amphetamine-antagonistic properties, as demonstrated by inhibition of methamphetamine (METH)-induced dopamine release in the nucleus accumbens and METH-induced hyperlocomotion in rats. In the present study, we examined the effect of PTIQ (10mg/kg, i.p.) and nomifensine (3mg/kg, i.p.) on METH (5 or 10mg/kg, i.p.)-induced stereotypical behavior in mice in order to determine whether PTIQ and nomifensine inhibit and augment, respectively, METH-induced stereotypical behavior. Unexpectedly, our observations demonstrated that both PTIQ and nomifensine significantly augmented METH-induced stereotypical behavior and locomotion in mice. This augmentation is likely the result of additive effects on dopaminergic function by METH in combination with PTIQ or nomifensine. These results suggest that, contrary to some reports, PTIQ may display dopaminergic agonist properties in mice.
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitanaka
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Nobue
authors.initials: N
authors.lastname: Kitanaka
authors.affiliation: Molecular Neurobiology Branch, National Institute on Drug Abuse-Intramural Research Program, Baltimore, Maryland 21224, U.S.A.
authors.forename: F Scott
authors.initials: FS
authors.lastname: Hall
authors.affiliation: Molecular Neurobiology Branch, National Institute on Drug Abuse-Intramural Research Program, Baltimore, Maryland 21224, U.S.A.
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Asano
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Ryuki
authors.initials: R
authors.lastname: Chatani
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hayata
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yokoyama
authors.affiliation: Division of Pharmacology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Hyogo 650-8530, Japan.
authors.forename: Koh-Ichi
authors.initials: KI
authors.lastname: Tanaka
authors.affiliation: Division of Pharmacology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Hyogo 650-8530, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Nishiyama
authors.affiliation: Department of Pharmacology, Hyogo College of Medicine, Hyogo 663-8501, Japan.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Takemura
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009627:Nomifensine / Q000494:pharmacology*; D011897:Random Allocation; D013239:Stereotyped Behavior / Q000187:drug effects*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
chemical_list: D015259:Dopamine Agents; D044005:Tetrahydroisoquinolines; D009627:Nomifensine; D008694:Methamphetamine; C074266:4-phenyl-1,2,3,4-tetrahydroisoquinoline