Cocaine and exercise: alpha-1 receptor blockade does not alter muscle glycogenolysis or blood lactacidosis.
In our previous work, we routinely observed that a combined cocaine-exercise challenge results in an abnormally rapid muscle glycogen depletion and excessive blood lactacidosis. These phenomena occur simultaneously with a rapid rise in norepinephrine and in the absence of any rise in epinephrine. We postulated that norepinephrine may cause vasoconstriction of the muscle vasculature through activation of alpha-1 receptors during cocaine-exercise, thus inducing hypoxia and a concomitant rise in glycogenolysis and lactate accumulation. To test this hypothesis, rats were pretreated with the selective alpha-1-receptor antagonist prazosin (P) (0.1 mg/kg iv) or saline (S). Ten minutes later, the animals were treated with cocaine (-C) (5 mg/kg iv) or saline (-S) and run for 4 or 15 min at 22 m/min at 10% grade. In the S-S group, glycogen content of the white vastus lateralis muscle was unaffected by exercise at both time intervals, whereas in S-C rats glycogen was reduced by 47%. This effect of cocaine-exercise challenge was not attenuated by P. Similarly, blood lactate concentration in S-C rats was threefold higher than that of S-S after exercise, a response also not altered by pretreatment with P. On the basis of these observations, we conclude that the excessive glycogenolysis and lactacidosis observed during cocaine-exercise challenge is not the result of vasoconstriction secondary to norepinephrine activation of alpha-1 receptors.
Conlee
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RK
Human Performance Research Center, Brigham Young University, Provo, Utah 84602, USA. robert_conlee@byu.edu
Kelly
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KP
Ojuka
E O
EO
Hammer
R L
RL
D000140:Acidosis, Lactic / Q000097:blood / Q000378:metabolism*; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D013997:Time Factors
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D019344:Lactic Acid; D006003:Glycogen; D003042:Cocaine; D011224:Prazosin