The effect of delta sleep-inducing peptide on the EEG and power spectra in rat.

The effects of delta sleep-inducing peptide (DSIP) on the EEG and power spectra of adult male Wistar rats (b.w. 180-220 g) were studied by power spectra analyses of EEG wave forms recorded continuously for 12 h after DSIP administration. The animals were given DSIP i.p. (1 mg/kg). Saline-injected rats served as the corresponding control. Recorded bursts of high amplitude EEG in the 1-9 Hz range (delta and theta) were found to be more frequent in DSIP-treated animals, while power spectra and (delta) wave activity were enhanced in comparison with the control and a statistically significant increase was registered in all experimental points after DSIP (2 h P < 0.05; 4 h P < 0.05; 5 h P < 0.05; 6 h P < 0.05; 7 h P < 0.01; 11 h P < 0.05). In addition, DSIP significantly elevated both the EEG output in the (delta) range and sleep activity. These results suggest that DSIP should be considered as a potential agent for the treatment of sleep disturbances in human medicine.

Metaphit-induced audiogenic seizure and its inhibition by MK-801: electroencephalographic and behavioral characterization.

Adult male Wistar rats were subjected to intense sound stimulation from an electric bell (100 dB and 12 KHz for 60 s) after a single intraperitoneal (i.p. 50 mg/kg) injection of metaphit [1-(1-/3 isothiocyanatophenyl-cyclohexyl) piperidine]. EEG recordings demonstrated appearance of paroxysmal activity and spike-wave complexes from cortical electrodes, with frequency and amplitude increasing with time. Metaphit-induced audiogenic seizures in the rats were tested 24 h after metaphit administration. The seizures consisted of wild running followed by clonic and tonic convulsions, and the seizure pattern could be elicited at hourly intervals for the next 24 h in all tested animals. Forty-eight hours after metaphit administration, susceptibility to sound stimulation began to decrease gradually. The first component of seizure response to disappear was tonic extension, followed by disappearance of clonic convulsion; the last component to disappear was running behavior. Each behavioral seizure response had a characteristic EEG correlate. After approximately 50 h, no animal responded to sound stimulation. The noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, MK-801 [5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine maleate] was evaluated as an anticonvulsant against metaphit-induced audiogenic seizures in two experiments. In the first experiment, MK-801 was administered in a single dose of 0.5 mg/kg i.p. 23.5 h after metaphit injection and 30 min before sound stimulation, which completely blocked both the EEG and the behavioral response to sound stimulation for 37 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Saturable mechanism for delta sleep-inducing peptide (DSIP) at the blood-brain barrier of the vascularly perfused guinea pig brain.

Cellular uptake of [125I] labelled DSIP at the luminal interface of the blood-brain barrier (BBB) was studied in the ipsilateral perfused in situ guinea pig forebrain. Regional unidirectional transfer constants (Kin) calculated from the multiple-time brain uptake analysis were 0.93, 1.33 and 1.66 microliter.min-1 g-1 for the parietal cortex, caudate nucleus and hippocampus, respectively. In the presence of 7 microM unlabelled DSIP the brain uptake of [125I]-DSIP (0.3 nM) was inhibited, the values of Kin being reduced to 0.23-0.38 microliter.min-1 g-1, values that were comparable with the Kin for mannitol. The rapidly equilibrating space of brain, measured from the intercept of the line describing brain uptake versus time on the brain uptake ordinate, Vi, was greater for [125I]-DSIP than for mannitol; in the presence of unlabelled DSIP this was reduced to that of mannitol, and it was suggested that the larger volume for [125I]-DSIP represented binding at specific sites on the brain capillary membrane. L-tryptophan, the N-terminal residue of DSIP, in concentrations of 7 microM and 1 mM, inhibited Kin without affecting Vi. A moderate inhibition of Kin was obtained by vasopressin ([Arg8]-VP), but only at a concentration as high as 0.2 mM. The results suggest the presence of a high affinity saturable mechanism for transport of DSIP across the blood-brain barrier, with subsequent uptake at brain sites that are highly sensitive to L-tryptophan, and may be modulated by [Arg8]-VP.