Antagonist precipitated clonidine withdrawal in rat: effects on locus coeruleus neurons, sympathetic nerves and cardiovascular parameters.
The goal of the present study was to examine the effect of clonidine withdrawal on the neural control of blood pressure. Rats were treated for 7-13 days with clonidine via osmotic minipumps (200 microg kg(-1) day(-1), s.c.). Controls received saline or were sham operated. Withdrawal was precipitated by the alpha2-adrenergic receptor (alpha2-AR) antagonist atipamezole. Most experiments were done under halothane anesthesia. Chronic treatment with clonidine did not change mean arterial pressure (MAP) or heart rate (HR) but raised femoral artery resistance and the activity of locus coeruleus neurons slightly. Atipamezole given to rats treated chronically with clonidine produced the following effects: no change in MAP, severe tachycardia, sustained increase in splanchnic sympathetic nerve discharge (SND; +75 +/- 13%), transient increase in lumbar SND (+23 +/- 7%), ON-OFF activity pattern in the locus coeruleus (LC). The ON phase of LC activity was synchronized with upswings of SND and with small changes in MAP. A second alpha2-AR antagonist, methoxyidazoxan, produced effects identical to those of atipamezole. Atipamezole given to control rats produced no effect on MAP, HR, SND or LC activity. Atipamezole reversed the hypotension, sympathoinhibition and bradycardia produced by acute administration of clonidine. In awake rats treated chronically with clonidine, atipamezole did not change MAP but produced arterial pressure lability and tachycardia. In conclusion, under anesthesia, selective alpha2-AR antagonists elicit a clonidine withdrawal syndrome that displays autonomic characteristics reminiscent of the spontaneous withdrawal syndrome found in awake rats. The most prominent features of this syndrome are tachycardia, sympathoactivation, lack of hypertension and an oscillating activity pattern of brainstem neurons leading to abrupt changes in SND and in MAP.[1]References
- Antagonist precipitated clonidine withdrawal in rat: effects on locus coeruleus neurons, sympathetic nerves and cardiovascular parameters. Grubb, M.C., Stornetta, R.L., Pence, R., Baertschi, A.J., Guyenet, P.G. J. Auton. Nerv. Syst. (1998) [Pubmed]
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