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melior melior melior discovery melior pharmaceuticals preclinical services pre-clinical services in vivo pharmacology in vivo efficacy efficacy models pharmacokinetics indications discovery specialized animal models bioanalytical services theratrace exton pennsylvania cro contract research drug discovery drug development metabolic disease alzheimer’s alzheimers diabetes reprofiling

Melior Discovery drug abuse liability

Locomotor Sensitization
An early indicator of abuse liability is increased locomotor activity and/or stereotypy.  Neurochemical studies have shown that locomotor stimulant effects of many psychostimulant drugs are related to dopamine and the dopaminergic system.  One behavioral effect correlated with repeat administration of psychostimulant drugs is sensitization to locomotor activity.  Thus, with repeat administration subjects demonstrate increased spontaneous locomotor activity following treatment.  Since behavioral sensitization serves as an important model of neural plasticity and has also been proposed as a model for a variety of psychiatric syndromes, including reward, therapeutics or novel compounds that result in locomotor sensitization or (cross-sensitization) to a known psychostimulant drug would potentially be an issue for both patient compliance and safety.

In our typical locomotor sensitization paradigm, animals are administered a test compound (or psychostimulant control or vehicle) over the course of 14 days.  Locomotor activity is recorded on days 1, 7 and 14.  Significant increases in locomotor activity (within-subject) over the course of the study is indicative of sensitization.  Cross-sensitization may be assessed by establishing sensitization to a known psychostimulant, then quantifying locomotor activity following acute administration of a test compound. 

 

                      

If you are interested in learning more about Locomotor Sensitization, please contact models@meliordiscovery.com to start the conversation.