Neurochemical and behavioral indices of exercise reward are independent of exercise controllability (2016)

Eur J Neurosci. 2016 Feb 1. doi: 10.1111/ejn.13193.

Herrera JJ1, Fedynska S2, Ghasem PR1, Wieman T1, Clark PJ1, Gray N2, Loetz E2, Campeau S3,4, Fleshner M1,4, Greenwood BN1,4.


Brain reward circuits are implicated in stress-related psychiatric disorders. Exercise reduces the incidence of stress-related disorders, but the contribution of exercise reward to stress resistance is unknown. Exercise-induced stress resistance is independent of exercise controllability; both voluntary and forced wheel running protect rats against anxiety- and depression-like behavioral consequences of stress. Voluntary exercise is a natural reward, but whether rats find forced wheel running rewarding is unknown. Moreover, the contribution of dopamine (DA) and striatal reward circuits to exercise reward is not well characterized.

Adult, male rats were assigned to locked wheels, voluntary running (VR), or forced running (FR) groups. FR rats were forced to run in a pattern resembling rats’ natural wheel running behavior.

Both VR and FR increased the reward-related plasticity marker ΔFosB in the dorsal striatum (DS) and nucleus accumbens (NAc), and increased activity of DA neurons in the lateral ventral tegmental area (VTA), as revealed by immunohistochemistry for tyrosine hydroxylase (TH) and pCREB.

Both VR and FR rats developed conditioned place preference (CPP) to the side of a CPP chamber paired with exercise.

Re-exposure to the exercise-paired side of the CPP chamber elicited conditioned increases in cfos mRNA in direct pathway (dynorphin-positive) neurons in the DS and NAc in both VR and FR rats, and in TH-positive neurons in the lateral VTA of VR rats only.

Results suggest that the rewarding effects of exercise are independent of exercise controllability and provide insight into the DA and striatal circuitries involved in exercise reward and exercise-induced stress resistance.

KEYWORDS: Dopamine; immediate early genes; rat; striatum; ventral tegmental area