Role of Src family kinase in the rewarding effect and hyperlocomotion induced by morphine.
The aim of the present study was to investigate the effect of a selective Src family kinase inhibitor, 4-amino-5-(4-chlorophenyl)-(t-butyl)pyrazolo[3,4-D]pyrimidine (PP2), on the rewarding effect and hyperlocomotion induced by morphine. An intracerebroventricular pretreatment with PP2 (0.1-10 nmol/mouse) significantly suppressed the morphine-induced rewarding effect and hyperlocomotion in a dose-dependent manner. We also investigated the changes in immunoreactivities to phosphorylated-Src family kinase in the nucleus accumbens of mice showing the morphine-induced rewarding effect. We found for the first time that Src family kinase is activated in the nucleus accumbens of mice showing the morphine-induced rewarding effect as compared with that found in saline-treated control mice. These findings suggest that Src family kinases in the nucleus accumbens are involved in the rewarding effect and hyperlocomotion induced by morphine.
Narita
Minoru
M
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. narita@hoshi.ac.jp
Kato
Hideaki
H
Kasukawa
Akiko
A
Narita
Michiko
M
Suzuki
Masami
M
Takeuchi
Tomoko
T
Suzuki
Tsutomu
T
D000818:Animals; D001522:Behavior, Animal; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007150:Immunohistochemistry / Q000379:methods; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D012201:Reward; D013997:Time Factors; D019061:src-Family Kinases / Q000378:metabolism / Q000502:physiology*
C412373:AG 1879; D009294:Narcotics; D011743:Pyrimidines; D009020:Morphine; D019061:src-Family Kinases