title: Cholinergic basal forebrain structures are involved in the mediation of the arousal effect of noradrenaline.
abstract: Cholinergic basal forebrain structures are implicated in cortical arousal and regulation of the sleep-wake cycle. Cholinergic neurones are innervated by noradrenergic terminals, noradrenaline excites them via alpha-1 receptors and microinjection of noradrenaline into the basal forebrain enhances wakefulness. However, it is not known to what extent the cholinergic versus non-cholinergic basal forebrain projection neurones contribute to the arousing effects of noradrenaline. To elucidate the roles of cholinergic basal forebrain structures we administered methoxamine, an alpha-1-adrenergic agonist into the basal forebrain, in intact animals and again after selective destruction of the basal forebrain cholinergic cells by 192 IgG-saporin. In eight male Han-Wistar rats implanted with electroencephalogram/electromyogram electrodes, a microdialysis probe targeted into the basal forebrain was perfused with artificial cerebrospinal fluid for 6 h on a baseline day, and with cerebrospinal fluid in the first and with methoxamine in the second 3-h period of the subsequent day. The sleep-wake activity was recorded for 24 h on both days. Saporin was then injected into the basal forebrain and 2 weeks later the same experimental schedule (with cerebrospinal fluid and methoxamine) was repeated. In the intact animals, methoxamine exhibited a robust arousing effect and non-rapid eye movement (NREM) and REM sleep was suppressed. Lesioning of the basal forebrain cholinergic neurones abolished almost completely the NREM sleep-suppressing effect of methoxamine, whereas the REM sleep-suppressing effect remained intact. Thus, the basal forebrain cholinergic neurones mediate, at least in part, cortical arousal and non-REM sleep-suppression, but they are not involved in the REM sleep-suppressing effects of noradrenaline.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Lelkes
authors.forename: Tarja
authors.initials: T
authors.lastname: Porkka-Heiskanen
authors.forename: Dag
authors.initials: D
authors.lastname: Stenberg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001143:Arousal / Q000187:drug effects* / Q000502:physiology*; D059329:Cholinergic Neurons / Q000187:drug effects* / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000008:administration & dosage / Q000494:pharmacology; D017551:Microdialysis; D009638:Norepinephrine / Q000494:pharmacology*; D016548:Prosencephalon / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage / Q000494:pharmacology; D000076985:Saporins; D012894:Sleep Stages / Q000187:drug effects* / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D008729:Methoxamine; D009638:Norepinephrine
keywords: alpha-adrenergic; arousal; basal forebrain; cholinergic lesion; sleep