The development of novel medications for CNS indications requires preclinical assessment of potential abuse liability. Rodent behavioral assessment of abuse liability is highly attractive due to its relatively low cost and high predictive validity. The following tests are offered by Creative Biolabs to assess the putative abuse liability of psychoactive drugs: specifically, conditioned place preference, drug discrimination, locomotor sensitization, and intravenous self-administration. As these assays provide insight into the potential abuse liability of new chemical entities as well as in vivo pharmacological mechanism(s) of action, they should form a key part of the development process for novel therapeutics aimed at treating CNS disorders.
Conditioned place preference is a procedure commonly used to assess the rewarding effects of a stimulus by measuring increased approach and contact behaviors. It is most commonly used in rodents as an indirect assessment of the rewarding effects of various classes of drugs, especially drugs of abuse. This test is based on Pavlovian conditioning, through which animals learn to associate a particular location with a particular stimulus in contrast to a location where the stimulus is absent.
Drug discrimination techniques are important tools for studying the in vivo pharmacology of drugs of abuse. These techniques involve establishing the interoceptive effects of a training drug with known abuse liability as a cue for performing a specific behavioral response. Typically, rats are trained daily during short sessions, in which lever pressing is reinforced by the presentation of food pellets. Measurements of the rat's behavior include the choice of levers, which means the percentage of responses on the drug-appropriate lever, and the rate of responding, which indicates the effects of the treatment.
Locomotor Sensitization
Repeated exposure to drugs of abuse results in a progressive and long-lasting enhancement of the locomotor response, a phenomenon termed psychomotor (or locomotor) sensitization. Many drugs that are abused, including cocaine and amphetamine. One remarkable aspect of this phenomenon is its duration as sensitized responses can be observed after several weeks, months, or up to at least a year of drug-free period. The emergence of locomotor sensitization in rodents treated with a novel compound indicates potential abuse liability of the compound.
Intravenous Self-Administration
Self-administration, an animal model of the reinforcing effects of drugs, has high predictive validity for drugs that are abused by humans for their euphoric effects. Consequently, intravenous (i.v.) self-administration has become the “gold standard” in preclinical assessment of abuse liability and is a primary method recommended by the U.S. Food and Drug Administration for use in screening novel compounds.
A key component in abuse liability testing is the appropriate evaluation of an objectively verified potential withdrawal or discontinuation syndrome induced by high dose chronic administration of the test article. The general approach to the evaluation of withdrawal is to treat subjects for a period of 2 to 3 weeks and then evaluate the occurrence of withdrawal syndrome for a sufficiently long time after drug discontinuation (at least 1 week). Withdrawal can either be assessed spontaneously upon cessation of dosing or can be precipitated following administration of a selective antagonist.
An extensive range of rodent neurological disease models is placed below for your review:
Creative Biolabs offers turn-key or a la carte services customized to our client's needs. The paradigms of these tests can be modified, and parameters can be added to suit your research requirements. Please contact us for more information if you are interested in our services.
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