Rapid Eye Movement Sleep and the Associated Cardiovascular Changes During and After Continuous 10-Day Infusion of Clonidine in Normotensive Rats

Abstract

The centrally acting alpha-adrenoceptor agonists clonidine, lofexidine, and S3341 vary in their selectivity for the alpha 2-adrenoceptor subtype (S3341 greater than clonidine greater than lofexidine). The aim of this study was to examine the frequency and duration of rapid eye movement (REM) sleep episodes, and the cardiovascular changes associated with these episodes, during and after the continuous (10-day) infusion of saline (0.9% wt/vol), clonidine (10 micrograms/kg/h), lofexidine (10 micrograms/kg/h), or S3341 (50 or 100 micrograms/kg/h) in unrestrained, chronically instrumented rats. During a typical 24-h period, the saline infusion animals (n = 4) had 46 +/- 3 REM sleep episodes of 2.4 +/- 0.1 min duration. The majority of these episodes were associated with relatively minor phasic and tonic changes in arterial blood pressure and heart rate. During infusion, the three drugs markedly reduced the cardiovascular and behavioural signs of REM sleep. On cessation of the clonidine and lofexidine infusions, rebound increases (i.e., to values greater than controls) in the frequency and duration of REM sleep episodes were observed. These episodes were associated with markedly exaggerated fluctuations in arterial blood pressure and heart rate. The REM sleep rebound and associated cardiovascular responses were greater during the post-lofexidine infusion phase. A relatively minor rebound increase in total REM sleep time was observed after cessation of the 100-micrograms/kg/h, but not the 50-micrograms/kg/h, infusion rate of S3341. The cardiovascular responses during the REM sleep episodes were mildly exaggerated after cessation of the higher infusion rate of S3341.(ABSTRACT TRUNCATED AT 250 WORDS)