Greco MA, Salin-Pascual R, Gerashchenko D, Blanco-Centurion C, Shiromani PJ (2001) Effects of 192-saporin lesion of the basal forebrain on sleep homeostasis and adenosine receptor (A1) mRNA levels. Neuroscience 2001 Abstracts 523.12. Society for Neuroscience, San Diego, CA.
Summary: Adenosine is hypothesized to be a mediator of sleep since adenosine levels in the basal forebrain increase after wakefulness and decrease following sleep. The inhibitory effect of adenosine on wake-active cholinergic neurons is thought to be mediated by the A-1 receptor subtype. We hypothesized that if adenosine inhibition of cholinergic neurons takes place via A-1A receptors on cholinergic neurons, the elimination of cholinergic cells should affect sleep homeostasis. To test this hypothesis, 192-saporin was used to selectively lesion basal forebrain cholinergic cells. 48h baseline sleep was recorded from male Sprague Dawley rats. Subsequently, the rats were kept awake for 12h and 24h recovery sleep was recorded. 192-saporin (4 ug) was then administered ICV. The rats were again continuously recorded for 3 weeks after the injection, a 12h prolonged waking period and during a 24h recovery sleep period. Brain sections processed for visualization of A1 mRNA and/or immunohistochemistry revealed that both ChAT- and parvalbumin-positive cells contained A-1A mRNA. 192-SAP eliminated ChAT immunoreactive cells in the basal forebrain. There were no differences in sleep-wakefulness up to 3 weeks after drug administration, a finding consistent with previous reports. In addition, there were no changes in recovery sleep following prolonged waking in lesioned rats. These results indicate that the cholinergic basal forebrain groups are not the primary mediators of wakefulness or of sleep homeostasis. We suggest that the effects of adenosine are mediated via binding to non-cholinergic neurons.
Related Products: 192-IgG-SAP (Cat. #IT-01)