Pretreatment with nomifensine or nomifensine analogue 4-phenyl-1,2,3,4- tetrahydroisoquinoline augments methamphetamine-induced stereotypical behavior in mice

Junichi Kitanaka, Nobue Kitanaka, F. Scott Hall, George R. Uhl, Hiromi Asano, Ryuki Chatani, Sachiko Hayata, Hiroko Yokoyama, Koh Ichi Tanaka, Nobuyoshi Nishiyama, Motohiko Takemura

Research output: Contribution to journalArticle

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 (10 mg/kg, i.p.) and nomifensine (3 mg/kg, i.p.) on METH (5 or 10 mg/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.

Original languageEnglish (US)
Pages (from-to)15-26
Number of pages12
JournalBrain Research
Volume1439
DOIs
StatePublished - Feb 23 2012
Externally publishedYes

Keywords

  • 4-Phenyl-1,2,3,4-tetrahydroisoquinoline
  • Methamphetamine
  • Nomifensine
  • Persistent locomotion
  • Stereotypical behavior

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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    Kitanaka, J., Kitanaka, N., Hall, F. S., Uhl, G. R., Asano, H., Chatani, R., Hayata, S., Yokoyama, H., Tanaka, K. I., Nishiyama, N., & Takemura, M. (2012). Pretreatment with nomifensine or nomifensine analogue 4-phenyl-1,2,3,4- tetrahydroisoquinoline augments methamphetamine-induced stereotypical behavior in mice. Brain Research, 1439, 15-26. https://doi.org/10.1016/j.brainres.2011.12.043