An Animal Model of Genetic Vulnerability to Behavioral Disinhibition and Responsiveness to Reward-Related Cues: Implications for Addiction methods

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    "name": "An Animal Model of Genetic Vulnerability to Behavioral Disinhibition and Responsiveness to Reward-Related Cues: Implications for Addiction methods",
    "description": "Protocol for An Animal Model of Genetic Vulnerability to Behavioral Disinhibition and Responsiveness to Reward-Related Cues: Implications for Addiction methods",
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        "position": 1,
        "name": "MATERIALS AND METHODS",
        "text": "A total of 260 male Sprague-Dawley rats from our selective breeding colony ( ) were used. Procedures were approved by the University Committee on the Use and Care of Animals. Unless otherwise indicated, rats were pair-housed and kept on a 12 h light/12 h dark cycle (lights on 0600 hours) with controlled temperature and humidity. Food and water were available ad libitum."
      },
      {
        "@type": "HowToStep",
        "position": 2,
        "name": "MATERIALS AND METHODS",
        "text": "Each generation of rats was screened for locomotor activity around 60 days of age (see; ). Novelty-induced locomotor data were also obtained for bHRs and bLRs from the S17 generation using an automated behavioral analysis system (CleverSys, Reston, VA; )."
      },
      {
        "@type": "HowToStep",
        "position": 3,
        "name": "General Statistics",
        "text": "Linear mixed-effects models ( ) were used to analyze the behavioral data. The covariance structure was explored and modeled appropriately for each dependent variable and when significant main effects or interactions were detected, Bonferroni post hoc comparisons were carried out. Independent t -tests were used to examine phenotypic differences in acquisition of behavior for the delay-discounting task and for the neurobiological data."
      },
      {
        "@type": "HowToStep",
        "position": 4,
        "name": "Impulsive behavior",
        "text": "DRL: The same rats used for the delay-discounting task were also used for the DRL task (adapted from. Test chambers were arranged such that there was just one lever located to either the right or left (counterbalanced) of the food cup and the lever remained extended for the duration of the sessions. Each 45 min session began with illumination of the house light and lever presentation. Rats were initially tested on a DRL-5-s schedule, in which a lever press resulted in illumination of the lever and pellet delivery only if at least 5 s had elapsed since the previous press. Following 5 days of training at DRL-5-s, the schedule was changed to DRL-10-s for 5 days, then to DRL-20-s for 5 days, and the last 5 days at DRL-30-s. The total number of lever presses and the total number of reinforcers (ie, successful lever presses) were recorded."
      },
      {
        "@type": "HowToStep",
        "position": 5,
        "name": "Response to quinpirole",
        "text": "Rats from the S17 generation received three doses of quinpirole (counterbalanced; 0.1, 0.3, and 1.0 mg/kg, i.p.) or three injections of vehicle (0.9% NaCL, i.p.). Behavior was videotaped during habituation and the post-injection period, and Clever Sys (Reston, VA) Drug Scan software was used to analyze video-recorded behavior (; )."
      },
      {
        "@type": "HowToStep",
        "position": 6,
        "name": "Cocaine US",
        "text": "shows the effect of pairing presentation of a lever-CS with an intravenous injection of cocaine (US) in bHR ( n =8) and bLR ( n =8) rats. With training, bHR rats developed a sign-tracking CR to the cocaine-paired CS, whereas bLR rats did not. It is important to note that with a drug US there is no measurable goal-tracking response-that is, there is no specific location associated with delivery of the cocaine. Moreover, when cocaine is used as the US, animals rarely contact the lever-CS (as they do with a food US). Instead, the sign-tracking CR consists of orientation to the lever followed by approach and exploration (often sniffing) in the immediate vicinity of the lever, similar to that described when rewarding electrical brain stimulation is used as the US (see; ). Thus, CS-directed approach behavior is illustrated in as the probability that a rat approached the lever during..."
      },
      {
        "@type": "HowToStep",
        "position": 7,
        "name": "Response to Quinpirole",
        "text": "The behavioral response to quinpirole, a direct agonist at D2/D3 dopamine receptors ( ), was assessed in bHR ( n =10-12/group) and bLR ( n =12/group) rats. Initial analysis of the time course of the behavioral effects indicated that the peak response fell between 25 and 55 min following injection, and therefore statistical analyses were conducted using data from this 30-min period. The effect of a saline injection was assessed in an independent group of animals and therefore these data were not included in the dose-effect analyses. However, independent t -tests were performed to determine whether the response at a specific dose significantly differed from that of the saline controls."
      },
      {
        "@type": "HowToStep",
        "position": 8,
        "name": "Response to Quinpirole",
        "text": "illustrates the dose-response functions for locomotor distance and the frequency of head movements following quinpirole administration. There was a significant effect of phenotype for quinpirole-induced locomotor activity (F (1,23) =9.99; P =0.01) and this effect was most pronounced at the lowest dose examined ( ). bHR rats exhibited a large increase in locomotor activity in response to 0.1 mg/kg of quinpirole relative to bLR rats and it was only at this lowest dose that bHR rats significantly differed from bHR saline control rats ( P =0.005). bLRs did not differ significantly from their saline control counterparts at any dose, but there was a trend level effect at 0.3 mg/kg ( P =0.09). There was also a trend for a phenotype × dose interaction (F (2,39) =2.67, P =0.08), but no overall effect of dose. These results were likely affected by the large amount of vari..."
      }
    ],
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    "isBasedOn": {
      "@type": "ScholarlyArticle",
      "headline": "An Animal Model of Genetic Vulnerability to Behavioral Disinhibition and Responsiveness to Reward-Related Cues: Implications for Addiction",
      "datePublished": "2010",
      "author": [
        {
          "@type": "Person",
          "name": "Shelly B Flagel"
        },
        {
          "@type": "Person",
          "name": "Terry E Robinson"
        },
        {
          "@type": "Person",
          "name": "Jeremy J Clark"
        },
        {
          "@type": "Person",
          "name": "Sarah M Clinton"
        },
        {
          "@type": "Person",
          "name": "Stanley J Watson"
        },
        {
          "@type": "Person",
          "name": "Phillip Seeman"
        },
        {
          "@type": "Person",
          "name": "Paul E M Phillips"
        },
        {
          "@type": "Person",
          "name": "Huda Akil"
        }
      ],
      "identifier": "10.1038/npp.2009.142"
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