Rapid eye movement sleep induction by microinjection of the GABA-A antagonist bicuculline into the dorsal subcoeruleus area of the rat.

In cats, rapid eye movement sleep (REMS) can be induced rapidly and reliably by injections of the cholinergic agonist carbachol into the anterodorsal pontine tegmentum, also recognized as the perilocus coeruleus alpha, and designated the REMS Induction Zone (RIZ). In rats, the RIZ has been ascribed to a much larger and more ventral region within the entire oral pontine reticular formation. However, carbachol injections throughout this area produce only small, unreliable, and long latency REMS enhancements. The present study investigated whether REMS induction in the rat is possible by microinjection into the dorsal subcoeruleus nucleus (SubCD), a region with similarities to the cat RIZ. In freely moving unanaesthetized rats, microinjection of the GABA-A antagonist bicuculline significantly increased the amount and reduced the latency to REMS during a 2-h recording in the mid-light period. However, at effective doses, bicuculline usually also produced intermittent ipsiversive circling behavior that disrupted REMS maintenance. Attempts at eliminating this side-effect by: (i) coinjection of bicuculline with the NMDA antagonist, APV, (ii) lower bicuculline doses, or (iii) injection of the GABA-B antagonist, phaclofen, were unsuccessful. Other drugs injected into this area did not induce REMS; these included carbachol, the acetylcholinesterase inhibitor neostigmine, the glutamate agonist kainate, and vasopressin. In the rat, the SubCD is a highly sensitive region for both REMS induction and locomotor effects.