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Adenosine and the homeostatic control of sleep: effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness.

Abstract

The orexinergic neurons of the lateral hypothalamus (LH) are critical for wakefulness [McCarley RW (2007) Neurobiology of REM and NREM sleep. Sleep Med 8:302-330]. Recent evidence suggests that adenosine (AD), a homeostatic sleep factor, may act via A1 receptor (A1R) to control orexinergic activity and regulate sleep-wakefulness [Thakkar MM, Winston S, McCarley RW (2002) Orexin neurons of the hypothalamus express adenosine A1 receptors. Brain Res 944:190-194; Liu ZW, Gao XB (2006) Adenosine inhibits activity of hypocretin/orexin neurons via A1 receptor in the lateral hypothalamus: a possible sleep-promoting effect. J Neurophysiol]. To evaluate the role of AD in the orexinergic LH and its influences on sleep-wakefulness, we designed two experiments in freely behaving rats: First, we bilaterally microinjected 1,3-dipropyl-8-phenylxanthine (DPX) (1.5 pmol and 15 pmol), a selective A1R antagonist into the LH during the light cycle and examined its effect on spontaneous sleep-wakefulness. Second, we performed 6 h of sleep deprivation. Thirty minutes before the animals were allowed to enter recovery sleep, 15 pmol of DPX was bilaterally microinjected into the LH and its effects on recovery sleep were monitored. Microinjection of DPX into the orexinergic LH produced a significant increase in wakefulness with a concomitant reduction in sleep, both during spontaneous bouts of sleep-wakefulness and during recovery sleep. Local administration of DPX into the LH produced a significant increase in the latency to non-REM sleep during recovery sleep. However, total slow wave (delta) activity during non-REM sleep phase of recovery sleep remained unaffected after DPX treatment. This is the first study that implicates endogenous adenosine to have a functional role in controlling orexinergic tone and influencing the homeostatic regulation of sleep-wakefulness.

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  • Authors+Show Affiliations

    ,

    Department of Neurology, University of Missouri, Harry S. Truman Veteran's Memorial Hospital, 800 Hospital Drive, Columbia, MO 65201-5297, USA. thakkarmm@health.missouri.edu

    , ,

    Source

    Neuroscience 153:4 2008 Jun 02 pg 875-80

    MeSH

    Adenosine
    Adenosine A1 Receptor Antagonists
    Analysis of Variance
    Animals
    Circadian Rhythm
    Delta Rhythm
    Dose-Response Relationship, Drug
    Homeostasis
    Hypothalamic Area, Lateral
    Male
    Microinjections
    Rats
    Rats, Sprague-Dawley
    Reaction Time
    Receptor, Adenosine A1
    Sleep
    Sleep Deprivation
    Time Factors
    Wakefulness
    Xanthines

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18440150

    Citation

    Thakkar, M M., et al. "Adenosine and the Homeostatic Control of Sleep: Effects of A1 Receptor Blockade in the Perifornical Lateral Hypothalamus On Sleep-wakefulness." Neuroscience, vol. 153, no. 4, 2008, pp. 875-80.
    Thakkar MM, Engemann SC, Walsh KM, et al. Adenosine and the homeostatic control of sleep: effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness. Neuroscience. 2008;153(4):875-80.
    Thakkar, M. M., Engemann, S. C., Walsh, K. M., & Sahota, P. K. (2008). Adenosine and the homeostatic control of sleep: effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness. Neuroscience, 153(4), pp. 875-80. doi:10.1016/j.neuroscience.2008.01.017.
    Thakkar MM, et al. Adenosine and the Homeostatic Control of Sleep: Effects of A1 Receptor Blockade in the Perifornical Lateral Hypothalamus On Sleep-wakefulness. Neuroscience. 2008 Jun 2;153(4):875-80. PubMed PMID: 18440150.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Adenosine and the homeostatic control of sleep: effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness. AU - Thakkar,M M, AU - Engemann,S C, AU - Walsh,K M, AU - Sahota,P K, Y1 - 2008/01/19/ PY - 2007/11/12/received PY - 2008/01/02/revised PY - 2008/01/04/accepted PY - 2008/4/29/pubmed PY - 2008/10/9/medline PY - 2008/4/29/entrez SP - 875 EP - 80 JF - Neuroscience JO - Neuroscience VL - 153 IS - 4 N2 - The orexinergic neurons of the lateral hypothalamus (LH) are critical for wakefulness [McCarley RW (2007) Neurobiology of REM and NREM sleep. Sleep Med 8:302-330]. Recent evidence suggests that adenosine (AD), a homeostatic sleep factor, may act via A1 receptor (A1R) to control orexinergic activity and regulate sleep-wakefulness [Thakkar MM, Winston S, McCarley RW (2002) Orexin neurons of the hypothalamus express adenosine A1 receptors. Brain Res 944:190-194; Liu ZW, Gao XB (2006) Adenosine inhibits activity of hypocretin/orexin neurons via A1 receptor in the lateral hypothalamus: a possible sleep-promoting effect. J Neurophysiol]. To evaluate the role of AD in the orexinergic LH and its influences on sleep-wakefulness, we designed two experiments in freely behaving rats: First, we bilaterally microinjected 1,3-dipropyl-8-phenylxanthine (DPX) (1.5 pmol and 15 pmol), a selective A1R antagonist into the LH during the light cycle and examined its effect on spontaneous sleep-wakefulness. Second, we performed 6 h of sleep deprivation. Thirty minutes before the animals were allowed to enter recovery sleep, 15 pmol of DPX was bilaterally microinjected into the LH and its effects on recovery sleep were monitored. Microinjection of DPX into the orexinergic LH produced a significant increase in wakefulness with a concomitant reduction in sleep, both during spontaneous bouts of sleep-wakefulness and during recovery sleep. Local administration of DPX into the LH produced a significant increase in the latency to non-REM sleep during recovery sleep. However, total slow wave (delta) activity during non-REM sleep phase of recovery sleep remained unaffected after DPX treatment. This is the first study that implicates endogenous adenosine to have a functional role in controlling orexinergic tone and influencing the homeostatic regulation of sleep-wakefulness. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/18440150/Adenosine_and_the_homeostatic_control_of_sleep:_effects_of_A1_receptor_blockade_in_the_perifornical_lateral_hypothalamus_on_sleep_wakefulness_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(08)00034-1 DB - PRIME DP - Unbound Medicine ER -