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Eszopiclone and zolpidem are hypnotics that differentially affect sleep and waking states in adult animals. Therefore, it was of interest to compare their effects on the states of sleep and wakefulness in aged animals.Our objective was to determine the responses to eszopiclone and zolpidem vis-à-vis sleep and waking states in aged guinea pigs and to compare them with the effects of these hypnotics in adult animals.Aged guinea pigs were prepared to monitor sleep and waking states and to perform a frequency analysis of the EEG. Eszopiclone and zolpidem were administered intraperitoneally (1, 3, and 10 mg/kg).Eszopiclone produced a more rapid and greater increase in NREM sleep as well as longer duration episodes of NREM sleep compared with zolpidem. There was also a significant increase in the latency to REM sleep with eszopiclone, but not with zolpidem. EEG power during NREM sleep increased in the delta band and decreased in the theta band following eszopiclone administration, whereas zolpidem had no effect on any of the frequency bands analyzed.In aged as well as adult guinea pigs, eszopiclone is a more effective hypnotic insofar as it produces a shorter latency to NREM sleep, a greater amount of NREM sleep and EEG delta waves. Differences in the effects produced by eszopiclone and zolpidem as a function of the aging process likely reflect the fact that they bind to different subunits of the GABAA receptors, which are differentially reactive to the aging process.

Hypocretinergic (orexinergic) neurons in the lateral hypothalamus project to motor columns in the lumbar spinal cord. Consequently, we sought to determine whether the hypocretinergic system modulates the electrical activity of motoneurons. Using in vivo intracellular recording techniques, we examined the response of spinal motoneurons in the cat to electrical stimulation of the lateral hypothalamus. In addition, we examined the membrane potential response to orthodromic stimulation and intracellular current injection before and after both hypothalamic stimulation and the juxtacellular application of hypocretin-1. It was found that (1) hypothalamic stimulation produced a complex sequence of depolarizing- hyperpolarizing potentials in spinal motoneurons; (2) the depolarizing potentials decreased in amplitude after the application of SB-334867, a hypocretin type 1 receptor antagonist; (3) the EPSP induced by dorsal root stimulation was not affected by the application of SB-334867; (4) subthreshold stimulation of dorsal roots and intracellular depolarizing current steps produced spike potentials when applied in concert to stimulation of the hypothalamus or after the local application of hypocretin-1; (5) the juxtacellular application of hypocretin-1 induced motoneuron depolarization and, frequently, high-frequency discharge; (6) hypocretin-1 produced a significant decrease in rheobase (36%), membrane time constant (16.4%), and the equalizing time constant (23.3%); (7) in a small number of motoneurons, hypocretin-1 produced an increase in the synaptic noise; and (8) the input resistance was not affected after hypocretin-1. The juxtacellular application of vehicle (saline) and denatured hypocretin-1 did not produce changes in the preceding electrophysiological properties. We conclude that hypothalamic hypocretinergic neurons are capable of modulating the activity of lumbar motoneurons through presynaptic and postsynaptic mechanisms. The lack of hypocretin-induced facilitation of motoneurons may be a critical component of the pathophysiology of cataplexy.