Abstract
Recent studies have shown that cocaine decreases, rather than increases sympathetic nerve discharge (SND). Whether these sympathoinhibitory responses are the result of cocaine's actions on monoaminergic transmission (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 actions on monoaminergic transmission are involved in mediating the sympathoinhibitory response to this drug. We examined the mean arterial pressure, heart rate and splanchnic sympathetic nerve responses elicited by cocaine (I mg/kg, i.v.) in pentobarbital-anesthetized rats depleted of 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 α-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 and significantly attenuated the pressor response and tachycardia elicited by tyramine (1 mg/kg, i.v.). In control rats, cocaine elicited marked (−64 ± 4%) and prolonged (44 ± 4 min) decreases in SND. The magnitude (−34 ± 11%) and duration (23 ± 6 min) of these responses were significantly attenuated after 1 day of monoamine depletion. After 2 days of depletion, the sympathoinhibitory response was abolished and was replaced by a small, brief increase in SND (l0 3%). The pressor responses were similar in control and depleted rats, while the bradycardic response (−33 ± 4 bpm) was significantly reduced after 1 and 2 days of monoamine depletion to −20 ± 3 and −15 ± 2 bpm, respectively. We conclude that a functionally intact monoaminergic system is essential for the sympathoinhibitory response to cocaine. Whether the pressor responses result from a non-monoaminergic or a reserpine and/or α-methyl- p-tyrosine resistant catecholaminergic mechanism is unknown.
Published Version
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