TY - JOUR
T1 - Pretreatment with nomifensine or nomifensine analogue 4-phenyl-1,2,3,4- tetrahydroisoquinoline augments methamphetamine-induced stereotypical behavior in mice
AU - Kitanaka, Junichi
AU - Kitanaka, Nobue
AU - Hall, F. Scott
AU - Uhl, George R.
AU - Asano, Hiromi
AU - Chatani, Ryuki
AU - Hayata, Sachiko
AU - Yokoyama, Hiroko
AU - Tanaka, Koh Ichi
AU - Nishiyama, Nobuyoshi
AU - Takemura, Motohiko
PY - 2012/2/23
Y1 - 2012/2/23
N2 - 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.
AB - 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.
KW - 4-Phenyl-1,2,3,4-tetrahydroisoquinoline
KW - Methamphetamine
KW - Nomifensine
KW - Persistent locomotion
KW - Stereotypical behavior
UR - http://www.scopus.com/inward/record.url?scp=84862830355&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862830355&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2011.12.043
DO - 10.1016/j.brainres.2011.12.043
M3 - Article
C2 - 22265332
AN - SCOPUS:84862830355
SN - 0006-8993
VL - 1439
SP - 15
EP - 26
JO - Brain Research
JF - Brain Research
ER -