Influence of chronic exercise on the amphetamine-induced dopamine release and neurodegeneration in the striatum of the rat.
The aim of this study was to verify the effect of chronic exercise on the striatal dopamine (DA) outflow induced by low and high single doses of amphetamine (AMPH), and verify the existence of an exercise protective role on neurodegeneration. Adult male Sprague-Dawley rats were randomly separated into six groups: chronic exercise, saline; chronic exercise, 5 mg kg(-1) AMPH; chronic exercise, 30 mg kg(-1) AMPH; without exercise, saline; without exercise, 5 mg kg(-1) AMPH; without exercise, 30 mg kg(-1) AMPH. Chronic exercise consisted of an 8-week running program on a treadmill, with increasing intensity. Animals were anesthetized, placed into a stereotaxic frame and an intracerebral guide cannula implanted into the caudate-putamen. When indicated, microdialysis was performed. Dialysate samples were collected during 30-min intervals for 6 h, before and after the intraperitonial administration of AMPH or saline solution. HPLC with electrochemical detection was used to quantify DA. Chronic exercise did not significantly change the extracellular DA basal values. Regarding the maximal DA levels in the dialysates, in the rats treated with 5 mg kg(-1) AMPH, there was no significant difference between groups with and without chronic exercise; on the contrary, in animals treated with 30 mg kg(-1) AMPH, the DA release was lower in the group with chronic exercise. Moreover, the maintenance of higher levels of DA along time in the training group suggests a diminished reuptake of DA. By using the Fluoro-Jade C staining technique, we did not find neuronal death in any of the groups. In conclusion, these results suggest that chronic exercise leads to a diminished release and reuptake of DA after administration of a high dose of AMPH, whereas neither chronic exercise nor AMPH seems to induce neurodegeneration.
Marques
Elsa
E
Department of Pharmacology, Biomedical Institute for Research on Light and Image (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Vasconcelos
Filipa
F
Rolo
Marta R
MR
Pereira
Frederico C
FC
Silva
Ana P
AP
Macedo
Tice R
TR
Ribeiro
Carlos F
CF
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D017551:Microdialysis; D009410:Nerve Degeneration / Q000139:chemically induced*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000697:Central Nervous System Stimulants; D000661:Amphetamine; D004298:Dopamine