In rats, injecting DSIP directly into the brain increased deep (slow‑wave) sleep, and other small molecules also changed sleep patterns. When DSIP was given together with muramyl dipeptide or uridine, the sleep effects were different from when each was given alone, showing that these substances can interact in complex ways.

Putative sleep substances were infused either singly or in combination into the third ventricle of freely behaving male rats for 10 h nocturnal period. The nocturnal amount of slow wave sleep (SWS) and paradoxical sleep (PS), and the number and duration of their episodes were compared to those of the previous night under saline infusion. The single administration revealed that each substance elicited partially differential and partially common sleep-modulatory activity. SWS was enhanced by the d-type of di-1-methylheptyl-2,5-dioxocyclohexane-1,4-dicarboxylate (d-DOC, 2.3 nmol), delta-sleep-inducing peptide (DSIP 2.5 nmol), deoxyuridine (0.1 nmol), muramyl dipeptide (MDP, 2.0 nmol), and prostaglandin D2 (PGD2, 0.36 nmol). Cytidine (10 pmol) increased the number of SWS episodes and reduced their duration, whereas deoxyguanosine (10 pmol) prolonged the duration. Deoxycytidine (10 pmol) and the 1-type of DOC (0.25 nmol) enhanced PS. Uridine (10 pmol) enhanced both SWS and PS. The simultaneous or sequential administration of DSIP, MDP and uridine resulted in a combination-dependent or sequence-dependent change in sleep-waking dynamics, which was quite different from the time-course sleep-modulation induced by the single administration of each substance. The results suggest that co-circulating sleep substances might interact at least in part, either synergistically or antagonistically, on the sleep-regulatory mechanism.