Anker Justin J, Gliddon Luke A, Carroll Marilyn E
Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Behav Pharmacol. 2008 Sep;19(5-6):615-29. doi: 10.1097/FBP.0b013e32830dc0ae.
The purpose of this study was to examine a form of impulsive behavior (impaired inhibition) using cocaine or food reward in addiction-prone and addiction-resistant rats that were bred for high saccharin (HiS) or low saccharin (LoS) intake, respectively. A Go/No-go procedure was used to examine cocaine and food reinforcement (Go component) and the inhibition of responding during a subsequent period of nonreward (No-go component). Rats were initially trained to self-administer intravenous cocaine (0.4 mg/kg) under an FR 1 schedule during daily Go/No-go sessions consisting of three components of cocaine reinforcement (Go) alternating with two nonreward components (No-go), each signaled by different stimuli. Responding and drug intake were compared under three FR values (FR 1, FR 3, and FR 5) and three cocaine doses (0.2, 0.4, and 0.8 mg/kg). A similar Go/No-go procedure was used with food reinforcement and the same three FR conditions. During the Go components for intravenous cocaine, female rats self-administered more infusions at the 0.2 and 0.4 mg/kg doses than males, indicating a sex difference in cocaine intake. During the No-go periods under the cocaine condition, HiS rats and females responded significantly more than LoS rats and males, indicating phenotype and sex differences in impaired inhibition. During the Go components with food reward, males responded more and earned more pellets than females, but there were no phenotype or sex differences in No-go responding (impulsivity). The results indicate that HiS rats and females are more prone than LoS rats and males to impulsive drug-seeking behavior.
本研究的目的是分别使用可卡因或食物奖励,在易成瘾和抗成瘾的大鼠中检验一种冲动行为形式(抑制受损),这些大鼠分别是为高糖精(HiS)或低糖精(LoS)摄入量而培育的。采用Go/No-go程序来检验可卡因和食物强化(Go成分)以及随后无奖励期(No-go成分)期间反应的抑制情况。大鼠最初在每天的Go/No-go实验中接受训练,在FR 1程序下自我注射静脉可卡因(0.4 mg/kg),该实验由可卡因强化的三个成分(Go)与两个无奖励成分(No-go)交替组成,每个成分由不同刺激信号指示。在三个FR值(FR 1、FR 3和FR 5)和三个可卡因剂量(0.2、0.4和0.8 mg/kg)下比较反应和药物摄入量。对食物强化采用类似的Go/No-go程序以及相同的三个FR条件。在静脉注射可卡因的Go成分期间,雌性大鼠在0.2和0.4 mg/kg剂量下自我注射的次数比雄性大鼠多,表明可卡因摄入量存在性别差异。在可卡因条件下的No-go期期间,HiS大鼠和雌性大鼠的反应明显多于LoS大鼠和雄性大鼠,表明在抑制受损方面存在表型和性别差异。在有食物奖励的Go成分期间,雄性大鼠的反应更多且获得的食丸更多,但在No-go反应(冲动性)方面没有表型或性别差异。结果表明,HiS大鼠和雌性大鼠比LoS大鼠和雄性大鼠更容易出现冲动性觅药行为。