Monoamine Transporter and Sodium Channel Mechanisms in the Rapid Pressor Response to Cocaine

Monoamine Transporter and Sodium Channel Mechanisms in the Rapid Pressor Response to Cocaine Intravenous (IV) cocaine (0.03–3 mg/kg) produced dose-dependent, rapid, and brief increases in blood pressure (BP) in conscious rats pretreated with the dopamine receptor antagonist, SCH 23390. Monoamine uptake inhibitors structurally analogous to cocaine (cocaethylene, CFT, βCIT, CPT, (+)-cocaine, norcocaine, and benztropine) also produced this rapid pressor response, whereas structurally unrelated uptake inhibitors with diverse monoamine transporter selectivities (BTCP, indatraline, GBR 12935, mazindol, nomifensine, and zimeldine) either did not produce a rapid pressor response or produced only a small pressor response. At nonconvulsant doses, the sodium channel blockers acetylprocainamide, dibucaine, dyclonine, prilocaine, proparacaine, quinidine, and tetracaine produced a small pressor response or no increase in BP. In rats implanted with telemetric devices, cocaine and its analog, CFT, produced a biphasic pharmacological response that consisted of an initial brief and abrupt behavioral arousal associated with a rapid, large increase in BP followed by prolonged, parallel increases in BP and locomotor activity. Pretreatment with SCH 23390 prevented the prolonged but not the initial rapid and brief pressor and activity responses to both cocaine and CFT administration. The present data suggest that the inhibition of dopamine, norepinephrine, or serotonin transporter functions, either alone or in combination, does not mediate the rapid pressor response to cocaine. The sodium channel-blocking action of cocaine per se does not appear to be involved in the rapid pressor response to cocaine. Finally, the present results confirm previous findings that dopaminergic mechanisms mediate the prolonged increases in BP and locomotor activity produced by cocaine. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pharmacology Biochemistry and Behavior Elsevier

Monoamine Transporter and Sodium Channel Mechanisms in the Rapid Pressor Response to Cocaine

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Publisher
Elsevier
Copyright
Copyright © 1998 Elsevier Science Inc.
ISSN
0091-3057
eISSN
1873-5177
D.O.I.
10.1016/S0091-3057(97)00448-6
Publisher site
See Article on Publisher Site

Abstract

Intravenous (IV) cocaine (0.03–3 mg/kg) produced dose-dependent, rapid, and brief increases in blood pressure (BP) in conscious rats pretreated with the dopamine receptor antagonist, SCH 23390. Monoamine uptake inhibitors structurally analogous to cocaine (cocaethylene, CFT, βCIT, CPT, (+)-cocaine, norcocaine, and benztropine) also produced this rapid pressor response, whereas structurally unrelated uptake inhibitors with diverse monoamine transporter selectivities (BTCP, indatraline, GBR 12935, mazindol, nomifensine, and zimeldine) either did not produce a rapid pressor response or produced only a small pressor response. At nonconvulsant doses, the sodium channel blockers acetylprocainamide, dibucaine, dyclonine, prilocaine, proparacaine, quinidine, and tetracaine produced a small pressor response or no increase in BP. In rats implanted with telemetric devices, cocaine and its analog, CFT, produced a biphasic pharmacological response that consisted of an initial brief and abrupt behavioral arousal associated with a rapid, large increase in BP followed by prolonged, parallel increases in BP and locomotor activity. Pretreatment with SCH 23390 prevented the prolonged but not the initial rapid and brief pressor and activity responses to both cocaine and CFT administration. The present data suggest that the inhibition of dopamine, norepinephrine, or serotonin transporter functions, either alone or in combination, does not mediate the rapid pressor response to cocaine. The sodium channel-blocking action of cocaine per se does not appear to be involved in the rapid pressor response to cocaine. Finally, the present results confirm previous findings that dopaminergic mechanisms mediate the prolonged increases in BP and locomotor activity produced by cocaine.

Journal

Pharmacology Biochemistry and BehaviorElsevier

Published: Feb 1, 1998

References

  • Sodium-sensitive cocaine binding to striatal membranes
    Kennedy, L.T; Hanbauer, I
  • Comparative effects of cocaine and pseudococaine on EEG activities, cardiorespiratory functions, and self-administration behavior in the rhesus monkey
    Matsuzaki, M; Spingler, P.J; Whitlock, E.G; Misra, A.L; Mule, S.J
  • Antagonism of behavioral effects of cocaine by selective dopamine receptor blockers
    Spealman, R.D
  • Possible novel pharmacodynamic action of cocaine
    Tella, S.R
  • SYSTAT
    Wilkinson, L

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