Exercise Modifies the Brain Metabolic Response to Chronic Cocaine Exposure Inhibiting the Stria Terminalis

Abstract

It is well known that exercise promotes health and wellness, both mentally and physiologically. It has been shown to play a protective role in many diseases, including cardiovascular, neurological, and psychiatric diseases. The present study examined the effects of aerobic exercise on brain glucose metabolic activity in response to chronic cocaine exposure in female Lewis rats. Rats were divided into exercise and sedentary groups. Exercised rats underwent treadmill running for six weeks and were compared to the sedentary rats. Using positron emission tomography (PET) and [18F]-Fluorodeoxyglucose (FDG), metabolic changes in distinct brain regions were observed when comparing cocaine-exposed exercised rats to cocaine-exposed sedentary rats. This included activation of the secondary visual cortex and inhibition in the cerebellum, stria terminalis, thalamus, caudate putamen, and primary somatosensory cortex. The functional network of this brain circuit is involved in sensory processing, fear and stress responses, reward/addiction, and movement. These results show that chronic exercise can alter the brain metabolic response to cocaine treatment in regions associated with emotion, behavior, and the brain reward cascade. This supports previous findings of the potential for aerobic exercise to alter the brain’s response to drugs of abuse, providing targets for future investigation. These results can provide insights into the fields of exercise neuroscience, psychiatry, and addiction research.

Exercise Influences the Brain’s Metabolic Response to Chronic Cocaine Exposure in Male Rats

“…The inhibition of regions outside of the frontal lobe could help correct the biased inhibition of the frontal lobe observed In humans and non-human primates following chronic cocaine use, particularly if regions are functionally connected to the frontal lobe. Furthermore, regions associated with motivated behavior have been shown to be modulated in our group's previous findings [8]. Inhibition in cPu, st, and the thalamus are of particular interest because they are a part of the brain's reward cascade [14], which may impact response to cocaine.…”

“…The frontal lobe itself is acutely affected by cocaine, and the effects persist the longest in the region during withdrawal. As previously mentioned, a range of sensorimotor regions have been shown to be inhibited in female rats exposed to chronic cocaine and chronic exercise [8]. The inhibition of regions outside of the frontal lobe could help correct the biased inhibition of the frontal lobe observed In humans and non-human primates following chronic cocaine use, particularly if regions are functionally connected to the frontal lobe.…”

“…In female Lewis rats, exercise has been shown to increase brain glucose metabolism in a range of sensorimotor regions [6][7][8]. In rats chronically exposed to cocaine, exercised rats showed activation in the secondary visual cortex, lateral area (V2L) compared to their sedentary counterparts [8,9].…”

“…In contrast, various sensorimotor regions have been observed to be inhibited in female rats exposed to both chronic exercise and chronic cocaine. BgluM inhibition has been observed in relation to the paraflocculus (PFL), the eighth cerebellar lobule (8cb), the paramedian lobule [2], the copula of the pyramis (COP), the stria terminalis (st), the stria medullaris of the thalamus, the medial and posteromedial parts of the bed nucleus of the stria terminalis (stmpm), the ventrolateral thalamic nucleus, (VL), the primary somatosensory cortex, hindlimb region (S1HL) [8].…”

“…Based on the previous literature, changes in basal ganglia activity associated with cocaine would be expected to be attenuated. The activation of the caudate putamen (striatum) (CPu) in chronically exercised female Lewis rats compared to sedentary controls [8] is of particular interest because the region is a part of the basal ganglia, which has been implicated in various aspects of cocaine-induced behavioral [18] effects. In female rats administered chronic cocaine in conjunction with the same exercise regimen as used in the current study, various regions of the basal ganglia were inhibited.…”