2-Phenylethylamine in combination with l-deprenyl lowers the striatal level of dopamine and prolongs the duration of the stereotypy in mice.
2-Phenylethylamine (PEA)-induced stereotypy in rodents is suggested to model psychotic symptoms of schizophrenia. It is reported that PEA induces dopamine release in the striatum in vivo and in vitro. The present study analyzed the PEA-induced stereotypy and possible associated brain dopamine metabolism in mice. Using male ICR mice treated with a combination of PEA (100 mg/kg, i.p.) and increasing doses of l-deprenyl (0-10 mg/kg, s.c.), we examined (1) the behavioral profile of stereotypy (rating the scores), and (2) the tissue levels of dopamine and its metabolites by high-performance liquid chromatography. The stereotypic scores reached a plateau level at 10 min which lasted until 30 min after a single administration of 100 mg/kg PEA. The stereotyped behavior completely disappeared 45 min after PEA administration. Pretreatment with l-deprenyl (0.1, 1, and 10 mg/kg, s.c.) dose-dependently prolonged the duration of PEA-induced stereotypy. Notably, pretreatment with l-deprenyl dose-dependently increased the continuous sniffing. Treatment with PEA in combination of l-deprenyl (1 and 10 mg/kg) significantly reduced the level of dopamine in the region of the striatum and nucleus accumbens, compared with control animals. These results suggest that PEA in combination with l-deprenyl prolonged the duration of the stereotypy (particularly, continuous sniffing) while reducing the striatal level of dopamine.
Kitanaka
Junichi
J
Department of Pharmacology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. kitanaka-hyg@umin.ac.jp
Kitanaka
Nobue
N
Tatsuta
Tomohiro
T
Takemura
Motohiko
M
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D012642:Selegiline / Q000008:administration & dosage / Q000494:pharmacology*; D013240:Stereotyping
D010627:Phenethylamines; D012642:Selegiline; C029261:phenethylamine; D004298:Dopamine