Locomotor Sensitization

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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 several days.  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. 

The study summarized below illustrates how cocaine yields increased locomotor activity upon each administration when administered repeatedly.

Cocaine increases locomoter activity, measured as distance travelled, in a dose-dependent manner.

Mice (N=6) were dosed (ip) with cocaine at either 5, 10, or 20 mg/kg daily over the course of 5 days. Locomotor activity was assessed over the course of one hour in an Open Field Activity chamber immediately after dosing. Data represent means ±SEM. * P < 0.05, ** P < 0.01, **** P < 0.0001 vs. Vehicle; ^^ P < 0.01, ^^^^ P < 0.0001 vs. Day 1

Locomotor Sensitization can be conducted in either mice or rats. Typical study designs involve study durations of about 1 week.