Striatal enkephalinergic differences in rats selectively bred for intrinsic running capacity

Abstract

Rats selectively bred for high- and low-capacity for running on a treadmill (HCR; LCR) also differ in wheel-running behavior, but whether wheel-running can be explained by intrinsic or adaptive brain mechanisms is not as yet understood. It is established that motivation of locomotory behavior is driven by dopaminergic transmission in mesolimbic and mesostriatal systems. However, whether voluntary wheel running is associated with enkephalinergic activity in the ventral striatum is not known. Materials & Methods 40 male (20 HCR and 20 LCR) and 40 female (20 HCR and 20 LCR) rats were randomly assigned to 3 weeks of activity wheel exposure or sedentary conditions without wheel access. After 3 weeks of activity-wheel running, rats were decapitated and brains were extracted. Coronal sections were analyzed utilizing in situ hybridization histochemistry for enkephalin (ENK) mRNA in the ventral striatum. Results HCR rats expressed less ENK than LCR rats in the nucleus accumbens among females (p <.01) and in the olfactory tubercle among both females (p <.05) and males (p<.05). There was no effect of wheel running on ENK mRNA expression. Conclusion Line differences in ENK expression in the olfactory tubercle, and possibly the nucleus accumbens, partly explain divergent wheel-running behavior. The lower striatal ENK in the HCR line is consistent with enhanced dopaminergic tone, which may explain the increased motivation for wheel running observed in the HCR line.

Effects of intrinsic aerobic capacity and ovariectomy on voluntary wheel running and nucleus accumbens dopamine receptor gene expression

“…Yet, an unexpected finding was that HCR OVX was the only group that did not increase weekly wheel running from week 1 to week 11. It has been shown that HCR have more than 5-fold greater voluntary running distance compared to LCR rats [9], and Booth’s group [18] previously proposed the possibility that rats selectively bred for high voluntary running are more physically active owing to their enhanced DA-associated transcriptomes in the NAc. Previous studies with mice also demonstrated that highly active mice express greater DA activation in the mesolimbic circuit compared to control mice [7, 19].…”

“…The large variations in motivated running behavior and locomotion between lines may be mediated by a unique brain pathway to engage motor behavior [8, 9]. The dopamine (DA) system in the mid-brain mesolimbic circuit has been considered a key controller for the regulation of motivation [10], reward [11], and motor control [12], that significantly contributes to voluntary physical activity.…”

Mu opioid receptor modulation in the nucleus accumbens lowers voluntary wheel running in rats bred for high running motivation

“…Werme et al (2002) found that running wheel access for 30 days reduces DFosB in NAc enkephalin-containing neurons, and selective overexpression of DFosB in striatal enkephalincontaining neurons decreased running. In rats selectively bred for high (HCR) and low running capacity (LCR), which also display high and low wheel running behavior, HCR rats expressed less Enk mRNA than LCR rats in the NAc; however this expression pattern was not altered after three weeks of wheel running (Monroe et al, 2014). The selection criteria for HCR and LCR was forced running during a treadmill test (Koch and Britton, 2001); thus differing from the selection criteria for voluntary running in our current study.…”

Sex‐dependent differences in voluntary physical activity

“…However, in the NAc of HVR and LVR rats, there is equal expression of Dr genes ( Dr 1 , 2 , and 5 ) and other genes examined, N4a2 , FosB , and BDNF . Examination of female and male rats bred for high and low-capacity to run on a treadmill (HCR and LCR, respectively) reveals that HCR rats express less encephalin ( Enk ) in the NAc and olfactory tubules than LCR rats, which is in line with increased dopaminergic tone and increased behavioral motivation in the latter group (Monroe et al 2014). Additional recent work suggests that estrogen-induced dopamine signaling in the NAc is positively correlated with voluntary PA in female rats bred for high fitness (Park et al Physiology & Behavior, Resubmitted ).…”