Effects of low dose cocaine on REM sleep in the freely moving rat

Abstract

Cocaine administration can be disruptive to sleep. In compulsive cocaine users, sleep disruption may be a factor contributing to relapse. The effects of cocaine on sleep, particularly those produced by low doses, have not been extensively studied. Low dose cocaine may stimulate brain reward systems that are linked to the liability of abusing of this drug. This study was designed to assess the effects of the acute administration of low to moderate cocaine doses on sleep in the rat. Polygraphic recordings were obtained from freely moving, chronically instrumented rats over a 6-h period after the administration of either cocaine (as a 2.5-10 mg/kg intraperitoneal dose) or saline. Following cocaine administration, time spent by the rats in wakefulness increased and slow wave sleep decreased in a dose-dependent manner, compared to controls. These changes lasted between 1 to 3 h following the cocaine administration. Rapid eye movement (REM) sleep was decreased during a 2- to 3-h period following the injection of 5 and 10 mg/kg doses of cocaine. In contrast, REM sleep increased during the periods 2-4 h after the administration of 2.5 and 5 mg/kg doses of cocaine. These results indicate that sleep can be significantly altered by low doses of cocaine when administered subacutely.

Figure 1

Effects of different doses of cocaine on percentages of wakefulness. Bar represents percentages (means and SD) of wakefulness every hour for a 6-h period of time after intraperitoneal injection of control vehicle (normal saline) and three different doses of cocaine. Note the significant dose-dependent increase of wakefulness after the cocaine injection. Note also that the low dose of cocaine-induced increase in wakefulness is significant only for 1 h. (□) control saline; ( ) 2.5 mg/kg cocaine, (■) 5.0 mg/kg cocaine; ( ) 10mg/kg cocaine. These P-values represent the comparison with control saline. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 2

Effects of different doses of cocaine on percentages of slow-wave sleep (SWS). Bar represents percentages (means and SD) of SWS every hour for a 6-h period of time after an intraperitoneal injection of the control vehicle (normal saline) and three different doses of cocaine. Note a significant dose-dependent reduction of slow-wave sleep after the cocaine administration. (□) control saline; ( ) 2.5 mg/kg cocaine, (■) 5.0 mg/kg cocaine; ( ) 10mg/kg cocaine. *P < 0.05, **P < 0.01, ***P < 0.001. These P-values represent the comparison with control saline.

Figure 3

Effects of different doses of cocaine on percentages of REM sleep. Bar represents percentages (means and SD) of REM sleep every hour for a 6-h period of time after intraperitoneal injection of control vehicle (normal saline) and three different doses of cocaine. Note a significant increase in REM sleep in the second, third, and fourth hours after the 2.5 mg/kg dose of cocaine injections. After the 5 mg/kg dose of cocaine injections total percentage of REM sleep was significantly less in the second hour due to the delayed onset of REM sleep, however, in the third, fourth and fifth hours the total percentage of REM sleep was significantly higher than the control. After the high dose (10 mg/kg) of cocaine, REM sleep was suppressed for four hours without an increase in the final two hours. (□) control saline; ( ) 2.5 mg/kg cocaine, (■) 5.0 mg/kg cocaine; ( ) 10mg/kg cocaine. *P < 0.05, **P < 0.01, ***P < 0.001. These P-values represent the comparison with control saline.