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Drug abuse

    Intravenous Self-Administration
    • Animals learn to lever press for an infusion of a compound, via an intravenous catheter. Measures reinforcing effects of drugs of abuse or potential addictive properties of new pharmacological compounds.
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    Intracranial Self-Stimulation

    • Animals lever press to stimulate brain regions involved in reward. Measures drug effects on reward.
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    Straight Alley

    • Animals run from a "start" box to a " goal" box, by way of a straight alley, to receive a drug infusion. Latency to reach the goal box reflects the motivation of the animal for the drug.
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    Place Conditioning

    • Evaluates preference or aversion of an animal for an environment that has been associated with a positive or negative stimulus, usually a mild shock or a drug. It is performed in a box with two distinguishable environments separated by an alley.
    • This test has been used to study learning and memory, as well as the reinforcing effects and potential addictive properties of drugs of abuse.
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    Locomotor Activity

    • Measured in activity boxes, in which photobeams measure locomotion. Changes in locomotor activity over repeated injections may reflect tolerance and sensitization to drug effects.
    • Apparatus : Activity cage
    • see : Activity

    Somatic and motivational withdrawal syndrome in rats

    • This set of experimental procedures allows (i) evaluation of physical and motivational symptoms of withdrawal as the measure of drug dependency, and (ii) evaluation of the effect of compounds on acquisition and expression of drug dependency. The test consists of two sets of experiments:
    • i) Naloxone induced conditioned place aversion; and ii) Naloxone induced withdrawal symptoms.If both measures are attenuated by a compound tested, it can be concluded that this compound is effective against the morphine dependency.
    • Apparatus : Naloxone-induced conditioned place aversion study is carried out in ten identical wooden chambers consisting of white and black arms (30x20x25 cm) with a different floor texture (plain wood or wire mesh) and a gray central area (12x20x25 cm). Black and white compartments are separated from the gray one by guillotine doors. ii) Naloxone-precipitated withdrawal syndrome study is carried out in five wired cages (20x20x25 cm).
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    Somatic and motivational withdrawal syndrome in mice

    • This set of experimental procedures allows (i) the evaluation of the effect of tested compounds on drug (opiate) - induced dependence [anti-addictive activity], and (ii) the evaluation of physical and motivational symptoms of withdrawal as the measure of the tested compound - induced dependence [addictive liability]. In the latter case, instead of morphine, a tested compound is used, to investigate if it may have addictive potential, similar to that produced by morphine. Both versions (regarded as independent projects) consists of two sets of experiments.
    • 1) Motivational aspects. The conditioned aversion (and/or its inhibition) is measured to assess whether a tested compound: (i) inhibits this aspect of morphine withdrawal, or (ii) mimics morphine addictive effect.
    • 2) Somatic aspects. Mice are rendered dependent on morphine (i), or a tested compound (ii). Upon naloxone challenge, the somatic aspects of withdrawal syndrome are investigated
    • If both withdrawal aspects are attenuated by a compound tested (version "i"), it can be concluded that the tested compound is effective against the morphine dependence. If both withdrawal effects are produced by a compound tested (version "ii"), it can be concluded that the tested compound may have addictive liability.
    • Regarding the version "i", (evaluation of the effect of tested compounds on drug (opiate) - induced dependence [anti-addictive activity]), the tested compound(s) may be given before naloxone challenge to study a possible effect on the expression of naloxone-precipitated conditioned place aversion. Alternatively, a tested compound may be given before each of morphine doses, to study if such a treatment may inhibit the development of morphine dependence. Numerous other modifications are possible and can be discussed with the investigator.
    • Apparatus : 1) Naloxone conditioned place aversion: A 3-compartment conditioned place aversion (CPA) test cage. 2) Naloxone induced withdrawal symptoms: Glass cylinders (10L).
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    Conditioned place preference/aversion in rats

    • Conditioned place preference/aversion procedure is used to evaluate reinforcing (i.e. rewarding/aversive) properties of drugs. Typically, in this paradigm animals are exposed to an apparatus with two distinctive environments. One environment is repeatedly associated with drug administration, while the other is paired with vehicle. Following training, the animals, usually drug free, are allowed to freely explore both environments, and the change in the time spent on the drug-paired side is measured. It is assumed that the animals learn to approach/avoid stimuli associated with the reward/aversion, and if they spend more/less time on the drug-paired side, the choice is attributed to the rewarding/aversive properties of the drug.
    • Conditioned place preference paradigm is extensively used to detect the abuse potential of psychoactive drugs and most drugs that are abused by humans (e.g. psychostimulants, opiates, benzodiazepines, alcohol) have been shown to support the conditioned preference. Place aversion conditioning allows detecting compounds that have aversive properties.
    • Apparatus : Training and tests are carried out in ten identical wooden chambers consisting of white and black arms (30x20x25 cm) with a different floor texture (plain wood or wire mesh) and a gray central area (12x20x25 cm). Black and white compartments are separated from the gray one by guillotine doors.
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    Conditioned place preference/aversion in mice

    • Conditioned place preference/aversion procedure is used to evaluate reinforcing (i.e. rewarding or aversive) properties of drugs. Typically, in this paradigm, animals are exposed to an apparatus with at least two distinctive environments. One environment is repeatedly associated with drug administration, while the other is paired with vehicle. Following training, the animals, usually drug free, are allowed to freely explore both environments, and the change in the time spent on the drug-paired side is measured. It is assumed that the animals learn to approach/avoid stimuli associated with the reward/aversion, and if they spend more/less time on the drug-paired side, the choice is attributed to the rewarding/aversive properties of the drug.
    • Conditioned place preference paradigm is extensively used to detect the abuse potential of psychoactive drugs and most drugs that are abused by humans (e.g., psychostimulants, opiates, benzodiazepines, alcohol) have been shown to support the conditioned preference. Place aversion conditioning allows detecting compounds which have aversive properties.
    • S. Heinrichs, F. Menzaghi, G. Schulteis, G. F. Koob, and L. Stinus. Suppression of corticotropin-releasing factor in the amygdala attenuates aversive consequences of morphine withdrawal. Behav.Pharmacol. 6:74-80, 1995.
    • Apparatus : A 3-compartment conditioned place preference (CPP) /aversion (CPA) test cage.
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