mTOR signalling in the nucleus accumbens shell is critical for augmented effect of TFF3 on behavioural response to cocaine.
Neuropeptides play important roles in modulating the rewarding value of abused drugs. Trefoil factor 3 (TFF3) was recently reported to modulate withdrawal syndrome of morphine, but the effects of TFF3 on the cocaine-induced behavioral changes are still elusive. In the present study, cocaine-induced hyperlocomotion and conditioned place preference (CPP) rat paradigms were provided to investigate the role of TFF3 in the reward response to cocaine. High-performance liquid chromatography (HPLC) analysis was used to analyse the dopamine concentration. The results showed that systemic TFF3 administration (0.1 mg/kg i.p.) significantly augmented cocaine- induced hyperlocomotion and CPP formation, without any effects on locomotor activity and aversive or rewarding effects per se. TFF3 significantly augmented the increment of the dopamine concentration in the NAc and the activity of the mTOR signalling pathway induced by acute cocaine exposure (10 mg/kg, i.p.) in the NAc shell, but not the core. The Intra-NAc shell infusion of rapamycin blocked TFF3-induced hyperactivity in cocaine-treatment rats. These findings indicated that TFF3 could potentiate behavioural response to cocaine, which may be associated with regulating dopamine concentration. Furthermore, the findings indicated that mTOR signalling pathway in the NAc shell is important for TFF3-induced enhancement on the cocaine-induced behavioral changes.
Department of Pharmacology, Medical School of Hunan Normal University, Changsha 410013, China.
Yi-Xiao
YX
Luo
Department of gynecology and obstetrics, Hebei General Hospital, Shijiazhuang 050051, China.
Hua
H
Han
Department of Senile Disease, the Third Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Juan
J
Shao
Department of Biochemistry and Molecular Biology, College of basic medicine, Hebei Medical University, Shijiazhuang 050017, China.
Yuan
Y
Gao
Department of Functional region of Diagnosis, Hebei Medical University Fourth Hospital, Hebei Medical University, Shijiazhuang 050011, China.
Xi
X
Yin
National Institute on Drug Dependence, Peking University, Beijing 100191, China.
Wei-Li
WL
Zhu
National Institute on Drug Dependence, Peking University, Beijing 100191, China.
Ying
Y
Han
Department of Biochemistry and Molecular Biology, College of basic medicine, Hebei Medical University, Shijiazhuang 050017, China.|National Institute on Drug Dependence, Peking University, Beijing 100191, China.
Hai-Shui
HS
Shi
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis; D006801:Humans; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000071165:Trefoil Factor-3 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D011994:Recombinant Proteins; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3; D058570:TOR Serine-Threonine Kinases; D003042:Cocaine; D004298:Dopamine