Microinjection of the 5-HT7 receptor antagonist SB-269970 into the rat brainstem and basal forebrain: site-dependent effects on REM sleep.

The effects of SB-269970, a selective 5-HT7 receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The 5-HT7 receptor ligand was microinjected into the horizontal limb of the diagonal band of Broca (HDB) and the laterodorsal tegmental nucleus (LDT) during the light period of the 12-h light/12-h dark cycle. For comparative purposes the compound was administered systemically and, in addition, injected directly into the dorsal raphe nucleus (DRN). Microinjection of SB-269970 into the HDB and the DRN induced a significant reduction of rapid-eye-movement sleep (REMS). Similar effects were observed after systemic administration of the 5-HT7 receptor antagonist. On the other hand, local infusion of the compound into the LDT provoked the opposite effect. It is proposed that the deactivation of GABAergic cells located in the HDB, DRN and LDT is responsible for the changes induced by SB-269970 on REM sleep values. It is suggested that the antidepressant effect of the 5-HT7 receptor antagonist could partly depend on the involvement of neuronal systems located in the DRN and the HDB.