Location of the mechanism of the clonidine withdrawal tachycardia in rats

J Pharm Pharmacol. 1985 Aug;37(8):580-2. doi: 10.1111/j.2042-7158.1985.tb03074.x.

Abstract

Withdrawal of chronic infusion of clonidine elicits severe tachycardia and short-lasting blood pressure elevations (upswings). Withdrawal of clonidine in low dosage (30 micrograms kg-1 day-1 i.c.v., 7 days) elicited a maximum of 10.9 +/- 0.5 upswings h-1. Cessation of s.c. infusion of clonidine (30 micrograms kg-1 day-1 7 days) evoked a maximum of 1.9 +/- 0.5 upswings h-1. After cessation of the two clonidine infusions no overshoot of heart rate occurred. Withdrawal of a higher dose of clonidine (300 micrograms kg-1 day-1 s.c., 7 days), however, induced tachycardia (from 302 +/- 8 to 433 +/- 8 beats min-1) and 7.6 +/- 1.4 upswings h-1. The administration of the alpha 2-adrenoceptor antagonist yohimbine precipitated withdrawal tachycardia in animals treated with oxymetazoline, a hydrophilic alpha-adrenoceptor agonist. Yohimbine (3 mg kg-1 i.p.) precipitated a severe rise in heart rate from 285 +/- 14 to 520 +/- 5 beats min-1 in oxymetazoline (300 micrograms kg-1 day-1 s.c., 7 days) treated rats and from 320 +/- 13 to 420 +/- 11 beats min-1 in saline-treated animals. Upswings were not induced by yohimbine treatment. It is concluded, that the blood pressure upswings after clonidine withdrawal are due to a central mechanism, whereas the mechanism of the overshoot of heart rate is located peripherally, probably at the cardiac presynaptic level.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Clonidine / toxicity*
  • Injections, Intraventricular
  • Injections, Subcutaneous
  • Male
  • Oxymetazoline / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Substance Withdrawal Syndrome / etiology*
  • Tachycardia / chemically induced*
  • Time Factors
  • Yohimbine / pharmacology

Substances

  • Yohimbine
  • Oxymetazoline
  • Clonidine