Systemic administration and local microinjection into the central nervous system of the 5-HT7 receptor agonist LP-211 modify the sleep-wake cycle in the rat

The effects of LP-211, a selective serotonin 5-HT7 receptor agonist were studied in adult rats implanted for chronic sleep recordings. Intraperitoneal administration of.LP-211 (2.5-10 mg/kg) during the light phase of the light-dark cycle significantly increased wakefulness (W) and reduced rapid-eye-movement sleep (REMS) and the number of REM periods during the 6-h recording period. Direct infusion of LP-211 into the dorsal raphe nucleus (DRN) (2-6 mM), locus coeruleus nucleus (LC) (4 mM), basal forebrain (horizontal limb of the diagonal band of Broca) (HDB) (2 mM) or laterodorsal tegmental nucleus (LDT) (4 mM) induced also a decrease of REMS. Additionally, microinjection of the 5-HT7 receptor ligand into the HDB (2 mM) augmented W. Presently, there is no satisfactory explanation for the effect of 5-HT7 receptor activation on Wand REMS occurrence. Additional studies are required to characterize the neurotransmitter systems responsible for the actions of LP-211 on the behavioral states. (C) 2013 Elsevier B.V. All rights reserved.