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-exercis e challenge results in an abnormally rapid muscle glycogen depletion and ex cessive blood lactacidosis. These Phenomena occur simultaneously with a rap id rise in norepinephrine and in the absence of any rise in epinephrine. We postulated that norepinephrine may cause vasoconstriction of the muscle va sculature 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 select ive 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 unaffecte d by exercise at both time intervals, whereas in S-C rats glycogen was redu ced 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 pretreatme nt with P. On the basis of these observations, we conclude that the excessi ve glycogenolysis and lactacidosis observed during cocaine-exercise challen ge is not the result of vasoconstriction secondary to norepinephrine activa tion of alpha-1 receptors.