TY - JOUR
T1 - Effects of hypocretin (orexin) neuronal loss on sleep and extracellular adenosine levels in the rat basal forebrain
AU - Murillo-Rodriguez, Eric
AU - Liu, Meng
AU - Blanco-Centurion, Carlos
AU - Shiromani, Priyattam J.
PY - 2008/9/1
Y1 - 2008/9/1
N2 - Neurons containing the neuropeptide hypocretin (HCRT, orexin) are localized only in the lateral hypothalamus, from where they innervate multiple regions implicated in arousal, including the basal forebrain. HCRT activation of downstream arousal neurons is likely to stimulate release of endogenous factors. One such factor is adenosine, which in the basal forebrain increases in level with wakefulness and decreases with sleep, and is hypothesized to regulate the waxing and waning of sleep drive. Does loss of HCRT neurons affect adenosine levels in the basal forebrain? Is the increased sleep that accompanies HCRT loss a consequence of higher adenosine levels in the basal forebrain? In the present study, we investigated these questions by lesioning the HCRT neurons with HCRT-2-saporin (HCRT-2-SAP) and measuring sleep and extracellular levels of adenosine in the basal forebrain. In separate groups of rats, the neurotoxin HCRT-2-SAP or saline was administered locally to the lateral hypothalamus, and 80 days later adenosine and sleep were assessed. Rats given the neurotoxin had a 94% loss of HCRT neurons. These rats woke less at night, and had more rapid eye movement sleep, which is consistent with HCRT hypofunction. These rats also had more sleep after brief periods of sleep deprivation. However, in the lesioned rats, adenosine levels did not increase with 6 h of sleep deprivation, whereas an increase in adenosine levels occurred in rats without lesion of the HCRT neurons. These findings indicate that adenosine levels do not increase with wakefulness in rats with a HCRT lesion, and that the increased sleep in these rats occurs independently of adenosine levels in the basal forebrain.
AB - Neurons containing the neuropeptide hypocretin (HCRT, orexin) are localized only in the lateral hypothalamus, from where they innervate multiple regions implicated in arousal, including the basal forebrain. HCRT activation of downstream arousal neurons is likely to stimulate release of endogenous factors. One such factor is adenosine, which in the basal forebrain increases in level with wakefulness and decreases with sleep, and is hypothesized to regulate the waxing and waning of sleep drive. Does loss of HCRT neurons affect adenosine levels in the basal forebrain? Is the increased sleep that accompanies HCRT loss a consequence of higher adenosine levels in the basal forebrain? In the present study, we investigated these questions by lesioning the HCRT neurons with HCRT-2-saporin (HCRT-2-SAP) and measuring sleep and extracellular levels of adenosine in the basal forebrain. In separate groups of rats, the neurotoxin HCRT-2-SAP or saline was administered locally to the lateral hypothalamus, and 80 days later adenosine and sleep were assessed. Rats given the neurotoxin had a 94% loss of HCRT neurons. These rats woke less at night, and had more rapid eye movement sleep, which is consistent with HCRT hypofunction. These rats also had more sleep after brief periods of sleep deprivation. However, in the lesioned rats, adenosine levels did not increase with 6 h of sleep deprivation, whereas an increase in adenosine levels occurred in rats without lesion of the HCRT neurons. These findings indicate that adenosine levels do not increase with wakefulness in rats with a HCRT lesion, and that the increased sleep in these rats occurs independently of adenosine levels in the basal forebrain.
KW - Adenosine
KW - Basal forebrain
KW - Microdialysis
KW - Orexin
KW - REM sleep
KW - Sleep
UR - http://www.scopus.com/inward/record.url?scp=51649126807&partnerID=8YFLogxK
U2 - 10.1111/j.1460-9568.2008.06424.x
DO - 10.1111/j.1460-9568.2008.06424.x
M3 - Artículo
C2 - 18783368
AN - SCOPUS:51649126807
SN - 0953-816X
VL - 28
SP - 1191
EP - 1198
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 6
ER -