The conditioned place preference (CPP) test is a standard pre-clinical behavioral tool used to study the motivational effects of drugs and non-drug treatments in experimental animals. The basic characteristic of this task involves the association of a particular environment and contextual cues with a reward stimulus, followed by the association of a different environment with the absence of the reward stimulus (Prus and Rosecrans, 2009). Besides the motor component, voluntary wheel running exercise also has a rewarding component, and has been suggested as a strong natural reinforcer. Consistent with this notion, rodents will readily begin to run when a wheel is introduced (Eikelboom and Mills, 1988; Looy and Eikelboom, 1989), will work by lever pressing to gain access to a running wheel (Pierce et al., 1986), and spend more time in a place previously associated with the aftereffects of running (Lett et al., 2000; Lett et al., 2001). More recently, we underscored an important role for the adipocyte-derived hormone leptin in midbrain dopamine neurons in the modulation of running reward (Fernandes et al., 2015). Here, we describe a CPP protocol to measure the rewarding aftereffects of wheel running exercise in mice.
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