Microinjection of the nitric oxide synthase inhibitor L-NAME into the lateral basal forebrain alters the sleep/wake cycle of the rat.

The effects of N(G)-nitro-L-arginine methyl ester (L-NAME) (0.19-0.74 micromol), a competitive inhibitor of the enzyme nitric oxide synthase (NOS); L-arginine (48.0-191.0 nmol), a nitric oxide (NO) precursor; and molsidomine (0.06-0.24 nmol), an NO donor, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. Direct bilateral application of L-NAME into the nucleus of the horizontal limb of the diagonal band of Broca (HDB) increased waking (W) and reduced slow wave sleep (SWS). On the other hand, intra-HDB injection of L-arginine or molsidomine induced slight but inconsistent changes of sleep variables that did not attain significance. Pretreatment with L-arginine (191.0 nmol) or molsidomine (0.24 nmol) prevented the increase of W and the reduction of SWS induced by L-NAME (0.37 micromol), thus indicating that a decrease in the availability of NO may be involved in the effects of L-NAME on sleep variables. An increase in the release of acetylcholine (ACh) and/or a reduction in the output of gamma-aminobutyric acid (GABA) and adenosine could tentatively explain the effects of L-NAME on SWS and W.