Treadmill running induces striatal Fos expression via NMDA glutamate and dopamine receptors

Abstract

Several non-physiological stimuli (i.e. pharmacological or electrical stimuli) have been shown to induce Fos expression in striatal neurons. In this work, striatal Fos (i.e. Fos-like) expression was studied after physiological stimulation, i.e. motor activity (treadmill running at 36 m/min for 20 min). In rats killed 2 h after the treadmill session, Fos expression was observed in the medial region of the rostral and central striatum, and in the dorsal region of the caudal striatum. Fos expression was prevented by pretreatment with the non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 (0.1 mg/kg) or the D1 dopamine receptor antagonist SCH-23390 (0.1 mg/kg), but not by pretreatment with the D2 receptor antagonist eticlopride (0.5 mg/kg). Thirty-six hours after 6-hydroxydopamine lesion, a considerable reduction in treadmill-induced Fos expression was observed in both sides; however, Fos expression in the lesioned striatum was higher than in the contralateral intact striatum. Several weeks after unilateral 6-hydroxydopamine lesion of the nigrostriatal system, treadmill-induced Fos expression was significantly, but not totally, reduced in the lesioned striatum. Corticostriatal deafferentation also led to considerable reduction in treadmill-induced Fos expression. The present results indicate that exercise induces striatal Fos expression and that, under physiological stimulation, concurrent activation of D1 and NMDA receptors is necessary for such expression to occur. Reduction of Fos expression is practically absolute after acute blockage of these receptors, but not after lesions, possibly due partially to compensatory changes.

Motor-Skill Learning-Associated Gene Regulation in the Striatum: Effects of Cocaine

“…Results showed that c-fos expression was enhanced in the dorsolateral striatum during the relearning phase (effect maximal on but not limited to the first day of gait change; Kitsukawa et al, 2002). However, similar to the above studies (Liste et al, 1997(Liste et al, , 1999, this effect was obtained immediately after wheel performance. In contrast, our finding of increased c-fos inducibility after running-wheel training under the influence of cocaine was obtained 24 h after the training.…”

“…However, it is unclear whether stress hormones modify cocaine-induced gene expression in the striatum (Barrot et al, 2001). On the other hand, running wheel-and locked wheel-trained rats differed considerably in their motor output during the training (running vs local movements), which could have contributed to differential molecular changes independent of motor learning (Liste et al, 1997(Liste et al, , 1999. However, our finding of a lack of differential c-fos induction after the 8-day training argues against a significant effect of motor output per se.…”

“…Only a few studies investigated the effects of running on gene expression in the striatum. These showed that the expression of c-fos, substance P, and enkephalin was increased in parts of the dorsal striatum immediately after treadmill running (Liste et al, 1997(Liste et al, , 1999. These effects were dependent on dopamine (D1) and glutamate (NMDA)/cortical inputs.…”

“…Liste et al (1997Liste et al ( , 1999 employed running on a straight motorized treadmill (fixed speed), which was practiced first (seven daily sessions) and was motivated by foot shocks. The wheel running study by Werme et al (2000) involved 30 days of unlimited access to the wheel from the home cage.…”

“…Moreover, according to previous studies, striatal regions (and midbrain dopamine neurons) display relatively minor or no c-fos induction by stressors (for reviews, see Senba and Ueyama, 1997;Kovacs, 1998;Pacak and Palkovits, 2001). Also, stress was ruled out as a major contributor to striatal c-fos induction during treadmill running (Liste et al, 1997). However, it is unclear whether stress hormones modify cocaine-induced gene expression in the striatum (Barrot et al, 2001).…”