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

Behavioral Pharmacology Laboratory, Boston University School of Medicine, Boston, Massachusetts, USA.
Sleep and Biological Rhythms (Impact Factor: 0.59). 02/2007; 5(1):55-62. DOI: 10.1111/j.1479-8425.2006.00247.x
Source: PubMed


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.

Download full-text


Available from: Domenic A Ciraulo
  • [Show abstract] [Hide abstract]
    ABSTRACT: Using extracellular single unit recordings alone or in combination with neurobiotin juxtacellular labeling and orexin (hypocretin) immunohistochemistry in the mouse, we have recorded a total of 452 neurons in the orexin neuron field of the posterior hypothalamus. Of these, 76 exhibited tonic discharge highly specific to wakefulness, referred to as waking-active neurons. They showed differences from each other in terms of spike shape, activity profile, and response to an arousing sound stimulus and could be classified into three groups on the basis of spike shape as: 1) biphasic broad; 2) biphasic narrow; and 3) triphasic. Waking-active neurons characterized by biphasic broad spikes were orexin-immunopositive, whereas those characterized by either biphasic narrow or triphasic broad spikes were orexin-immunonegative. Unlike waking-specific histamine neurons, all orexin and non-orexin waking-active neurons exhibited slow (<10 Hz) tonic discharges during wakefulness and ceased firing shortly after the onset of electroencephalogram (EEG) synchronization (deactivation), the EEG sign of sleep (drowsy state). They remained virtually silent during slow-wave sleep, but displayed transient discharges during paradoxical (or rapid eye movement) sleep. During the transition from sleep to wakefulness, both orexin and triphasic non-orexin neurons fired in clusters prior to the onset of EEG activation, the EEG sign of wakefulness, and responded with a short latency to an arousing sound stimulus given during sleep. In contrast, the biphasic narrow non-orexin neurons fired in single spikes either prior to, or after, EEG activation during the same transition and responded to the stimulus with a longer latency. The activity of all waking-active neurons preceded the return of muscle tonus at the transition from paradoxical sleep to wakefulness. These data support the view that the activity of orexin and non-orexin waking-active neurons in the posterior hypothalamus plays an important wake-promoting role and that their activity antagonizes cortical deactivation and loss of muscle tone.
    No preview · Article · May 2008 · Neuroscience
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The mesolimbic dopaminergic system (ML-DA) allows adapted interactions with the environment and is therefore of critical significance for the individual's survival. The ML-DA system is implicated in reward and emotional functions, and it is perturbed in schizophrenia, addiction, and depression. The ML-DA reward system is not only recruited during wakeful behaviors, it is also active during sleep. Here, we introduce the Reward Activation Model (RAM) for sleep and dreaming, according to which activation of the ML-DA reward system during sleep contributes to memory processes, to the regulation of rapid-eye movement (REM) sleep, and to the generation and motivational content of dreams. In particular, the engagement of ML-DA and associated limbic structures prioritizes information with high emotional or motivational relevance for (re)processing during sleep and dreaming. The RAM provides testable predictions and has clinical implications for our understanding of the pathogenesis of major depression and addiction.
    Full-text · Article · Jun 2012 · Neuroscience & Biobehavioral Reviews
  • [Show abstract] [Hide abstract]
    ABSTRACT: RATIONALE: Clinical trials show that chronic cocaine users suffer from sleep disturbances and preclinical research has shown that acute sleep deprivation increases the rate of cocaine self-administration in rats. OBJECTIVE: This study examined the effect of cocaine self-administration on behavioral indices of sleep and alternatively the effect of sleep disruption on cocaine-maintained responding by rhesus monkeys. METHODS: Seven adult rhesus monkeys, fitted with Actical® activity monitors, were trained to respond under a concurrent choice paradigm with food (three 1.0-g pellets) and cocaine (0.003-0.3 mg/kg) or saline presentation. For each monkey, the lowest preferred dose of cocaine (>80 % cocaine choice) was determined. Activity data were analyzed during lights out (2000-0600) to determine sleep efficiency, sleep latency, and total activity counts. Subsequently, the monkeys' sleep was disrupted (every hour during lights-out period) the night prior to food-cocaine choice sessions. RESULTS: Self-administration of the preferred dose of cocaine resulted in a significant decrease in sleep efficiency, with a significant increase in total lights-out activity. Sleep disruption significantly altered behavioral indices of sleep, similar to those seen following cocaine self-administration. However, sleep disruption did not affect cocaine self-administration under concurrent choice conditions. CONCLUSIONS: Based on these findings, cocaine self-administration does appear to disrupt behavioral indices of sleep, although it remains to be determined if treatments that improve sleep measures can affect future cocaine taking.
    No preview · Article · Apr 2013 · Psychopharmacology