Physical Activity Motivation: are Nucleus Accumbens Dopamine and Opioid Signaling Involved

Abstract

Neuro‐molecular mechanisms that regulate physical activity motivation are poorly understood. The mesolimbic dopamine system has been postulated to influence rewarding behaviors and may be involved in the central control of physical activity motivation. Therefore, we investigated 1) differences in nucleus accumbens (NAc) mRNA expression of dopamine‐related genes in rats selectively bred for low motivation for voluntary running (LVR) versus high motivation for voluntary running (HVR) behavior after 9 weeks of voluntary wheel running or being sedentary (n=8 per group), and 2) how NAc opioid receptor mu1 (Oprm1) modulation impacts nightly running behavior in LVR rats (n=7). On average, HVR with wheels ran significantly further (23.88 ± 6.69 vs. 2.56 ± 0.45 km/day), longer (387.60 ± 14.94 vs. 60.48 ± 9.91 min/day), and faster (61.73 ± 1.25 vs. 41.91 ± 2.45 m/min) than LVR. Relative mRNA levels of the dopamine‐related genes dopamine receptor1 (Drd1), Drd2, Drd5, tyrosine hydrolase, and protein kinase inhibitor a were significantly decreased in LVR vs. HVR, regardless of running wheel availability. Similarly, Oprm1 mRNA level was ~4.3‐fold lower in the LVR vs. HVR (p < 0.001). Surprisingly, no differences in other dopamine‐target genes were observed between LVR and HVR. In LVR, NAc injection of the Oprm1 agonist DAMGO decreased running for the entire dark‐cycle and for hours 4‐12 of the dark cycle (p < 0.05) at a dose of 2.5μg per side, but not with 0.25μg per side. Oprm1 antagonist naltrexone injection (5, 10, and 20μg per side) had no significant impact on running behavior. In conclusion, mRNA level differences related to NAc dopamine and opioid function between LVR and HVR may account for differences in physical activity motivation, and modulation of opioid signaling may alter voluntary running behavior.