THE DEPLETION OF MONOAMINES BLOCKS THE SYMPATHOINHIBITORY RESPONSE TOCOCAINE

Recent studies have shown that cocaine decreases, rather than increase s sympathetic nerve discharge (SND). Whether these sympathoinhibitory responses are the result of cocaine's actions on monoaminergic transmi ssion (i.e. blockade of neuronal uptake or stimulation of transmitter release) or its local anesthetic actions is not known. The purpose of the present study was to determine the degree to which cocaine's actio ns on monoaminergic transmission are involved in mediating the sympath oinhibitory response to this drug. We examined the mean arterial press ure, heart rate and splanchnic sympathetic nerve responses elicited by cocaine (1 mg/kg, i.v.) in pentobarbital-anesthetized rats depleted o f monoamines. Monoamines were depleted by administering reserpine (10 mg/kg, i.p.) either 24, or 48 and 24 h before the experiment. The rats were also given alpha-methyl-p-tyrosine (200 mg/kg, i.p.) 2 h before the experiment. Vehicle-treated rats served as controls. Depletion of monoamines markedly reduced resting arterial pressure and heart rate a nd significantly attenuated the presser response and tachycardia elici ted by tyramine (1 mg/kg, i.v.). In control rats, cocaine elicited mar ked (- 64 +/- 4%) and prolonged (44 +/- 4 min) decreases in SND. The m agnitude (- 34 +/- 11%) and duration (23 +/- 6 min) of these responses were significantly attenuated after 1 day of monoamine depletion. Aft er 2 days of depletion, the sympathoinhibitory response was abolished and was replaced by a small, brief increase in SND (10 +/- 3%). The pr esser responses were similar in control and depleted rats, while the b radycardic response (- 33 +/- 4 bpm) was significantly reduced after 1 and 2 days of monoamine depletion to - 20 +/- 3 and - 15 +/- 2 bpm, r espectively. We conclude that a functionally intact monoaminergic syst em is essential for the sympathoinhibitory response to cocaine. Whethe r the presser responses result from a non-monoaminergic or a reserpine and/or alpha-methyl-p-tyrosine resistant catecholaminergic mechanism is unknown.