Modulation of desynchronized sleep through microinjection of beta-adrenergic agonists and antagonists in the dorsal pontine tegmentum of the cat.
Brain noradrenergic systems have often been implicated in the regulation of desynchronized sleep (DS). In particular, the reciprocal interaction model of DS generation postulates that noradrenergic neurons in the locus coeruleus inhibit DS-executive cells located in the pontine reticular formation. Accordingly, since noradrenergic inhibition is generally mediated by beta-receptors, one should expect beta-agonists to decrease and beta-antagonists to increase DS. However, systemic injection experiments yielded just the opposite results. Assuming that local microinjection techniques were better suited to testing the model, beta-agonists and antagonists were directly infused into the dorsal pontine tegmentum (DPT), a region crucially implicated in the generation of DS. Cats were implanted with standard electrodes for polygraphic recordings and with guide tubes for chemical microinjections. It was observed that, when injected into the DPT, the beta-agonist isoproterenol almost suppressed DS, while the beta-antagonist propranolol consistently enhanced it, the latter largely due to an increased number of DS episodes. These effects were dose-dependent and strictly site-specific, since injections in immediately neighbouring structures were ineffective. These results: (a) confirm that cell groups located in the DPT play a key role in the generation of DS, and (b) indicate that they undergo a strong noradrenergic modulation, being inhibited by beta-receptor stimulation and disinhibited by beta-receptor blockade as predicted by the reciprocal interaction model.
Tononi
G
G
Dipartimento di Fisiologia e Biochemica, Universita' di Pisa, Italy.
Pompeiano
M
M
Pompeiano
O
O
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D005260:Female; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D011149:Pons / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D007545:Isoproterenol