Rapid eye movement sleep induction by vasoactive intestinal peptide infused into the oral pontine tegmentum of the rat may involve muscarinic receptors

In rats, rapid eye movement sleep can be induced by microinjection of eithe r the cholinergic agonist carbachol or the neuropeptide vasoactive intestin al peptide into the oral pontine reticular nucleus. Possible involvement of cholinergic mechanisms in the effect of vasoactive intestinal peptide was investigated using muscarinic receptor ligands. Sleep-waking cycles were an alysed after infusion into the oral pontine reticular nucleus of vasoactive intestinal peptide (10 ng in 0.1 mu l), carbachol (20 ng), atropine (200 n g) and pirenzepine (50, 100 ng), performed separately or in combination at 15-min intervals. The increase in rapid eye movement sleep due to the combi ned infusion of vasoactive intestinal peptide and carbachol (+58.7+/-4.6% f or 8 h, P<0.05) was not significantly different from that induced by each c ompound separately. The enhancement of rapid eye movement sleep by vasoacti ve intestinal peptide was totally prevented by infusion of atropine, but no t pirenzepine, a relatively selective M-1 antagonist. On their own, none of the latter two compounds affected the sleep-waking cycle. Quantitative aut oradiographic studies using [H-3]quinuclidinyl benzylate (1 nM) and pirenze pine (0.5 mu M) indicated that muscarinic receptors correspond to pirenzepi ne-insensitive binding sites in the oral pontine reticular nucleus. lit vit ro, vasoactive intestinal peptide (1-100 nM) significantly increased (+30-4 0%) the specific binding of [H-3]quinuclidinyl benzylate to the oral pontin e reticular nucleus in rat brain sections. This effect appeared to be due t o an increased density, with no change in affinity, of pirenzepine-insensit ive binding sites in this area. These data suggest that pirenzepine-insensitive muscarinic binding sites ar e involved in the induction of rapid eye movement sleep by vasoactive intes tinal peptide at the pontine level in the rat. (C) 1998 IBRO. Published by Elsevier Science Ltd.