Intra-ventral tegmental area injection of rat cocaine and amphetamine-regulated transcript peptide 55-102 induces locomotor activity and promotes conditioned place preference

作     者：Kimmel, HL Gong, WH Dall Vechia, S Hunter, RG Kuhar, MJ 

作者机构：Emory Univ Yerkes Reg Primate Res Ctr Atlanta GA 30329 USA 

出 版 物：《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)

年 卷 期：2000年第294卷第2期

页      面：784-792页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：NCRR NIH HHS [RR00165] Funding Source: Medline NIDA NIH HHS [DA00418, DA10732] Funding Source: Medline 

主　　题：选择行为/药物作用 条件反射 操作式/药物作用 注射 脑室内 行走/药物作用 运动活动/药物作用 神经组织蛋白质类/投药和剂量 肽碎片/投药和剂量 大鼠 Sprague-Dawley 腹侧被盖区/解剖学和组织学 腹侧被盖区/药物作用 腹侧被盖区/生理学 动物 男(雄)性 大鼠 

摘      要：Cocaine- and amphetamine-regulated transcript (CART) is a novel mRNA that has been reported to be increased by acute psychostimulant administration, and that may be involved in the effects of psychostimulants. In this study, we examined the effect of centrally administered CART peptides on locomotor activity and conditioned place preference in the rat. CART peptide fragments were bilaterally injected into the ventral tegmental area. CART 55-102 (0.2-5.0 mu g/side), an endogenously occurring peptide, dose dependently increased locomotor activity, whereas CART 1-26 (0.1-2.5 mu g/side;not found endogenously) did not. The locomotor effects of CART 55-102 were dose dependently blocked by the dopamine D-2 receptor antagonist haloperidol (0.03-1.0 mg/kg i.p.). Four injections of 1.0 mu g/side CART 55-102 induced a significant place preference, suggesting that CART 55-102 is reinforcing. Increases in locomotor activity after each of these CART 55-102 injections were similar and did not show tolerance or sensitization. This treatment regimen of CART 55-102 also did not produce sensitization to locomotor activity after a subsequent challenge with cocaine or amphetamine. When CART 55-102 (0.2-1.0 mu g/side) was injected into the substantia nigra, no significant change in motor activity was observed. However, a higher dose of CART 55-102 (5.0 mu g/side) induced a delayed increase in motor activity, suggesting a possible diffusion from the substantia nigra into the ventral tegmental area. Our findings suggest that CART 55-102 is behaviorally active and may be involved in the actions of psychostimulants. This is the first demonstration of the psychostimulant-like effects of CART peptides.