Neuropeptide trefoil factor 3 increases reward effects of cocaine in rats

Abstract

Objective To investigate the role of neuropeptide trefoil factor 3 (TFF3) in cocaine reward responses and the underlying mechanism. Methods Fifty SD rats were divided into 6 groups including Control group, Cocaine group, Cocaine + TFF3 (0.01 mg/kg)group, cocaine + TFF3 (0.1 mg/kg)group, cocaine + TFF3 (0.5 mg/kg)group and TFF3 (0.1 mg/kg)group, ip, n=7~9), and were treated with TFF3 / saline (ip), 30 min later, rats were injected with cocaine (10 mg/kg ip) followed by 1 h hyperlocomotion test. Immediately after behavioral test, rats (n=4~6) were decapitated and tissues of nucleus accumbens (NAc) were isolated and prepared for neurotransmitters analysis by HPLC; Another twenty one rats were divided into control and TFF3-treatment group, and the rats were trained with a modified 2-day cocaine CPP conditioning procedure. During cocaine CPP conditioning process, saline or TFF3 (0.1 mg/kg ip) was injected 30 min prior to cocaine injection (5 mg/kg ip). Results Systemic administration of TFF3 (0.1 mg/kg, ip) significantly increased the cocaine-induced locomotor activity (Total distance in 1 hour were (180±41) cm, (359±53) cm, (590±75) cm, (153±27) cm for Control, Vehicle + Cocaine, TFF3+ Cocaine and TFF3+ Vehicle groups respectively) and augmented cocaine rewarding effects in CPP(Post-training CPP score were (98±18) s, (187±24) s for Vehicle + Cocaine, TFF3+ Cocaine groups respectively). TFF3 (0.1 mg/kg ip) administration increased the dopamine concentration in the NAc induced by cocaine injection((0.65±0.1) ng/ml, (1.24±0.14) ng/ml, (1.75±0.23) ng/ml, (0.74±0.21) ng/ml for Control, Cocaine, TFF3+ Cocaine and TFF3+ Vehicle groups respectively). Conclusion TFF3 is involved in regulation of behavioral response to cocaine, which is associated with the increasing of dopamine in the NAc. Key words: Drug addiction; Neuropeptide; Trefoil factor 3; Cocaine reward; Dopamine