Paper description: Efficient drug treatment for resistant forms of epilepsy still haven’t been found. Lindane-induced seizures are refractory to numerous classical antiepileptic drugs. Delta sleep inducing peptide (DSIP) is a neuroprotective nonapeptide capable of optimizing the excitation/inhibition relationship. It is not known whether DSIP is capable of modulating refractory seizures. In our work we demonstrated by behavioral and electroencephalographic studies that DSIP can beneficially modulate the severity of lindane-induced seizures and ictal period frequency. DSIP has the potential to be an add-on component in antiepileptic treatment strategy for refractory seizures. Abstract: Delta sleep-inducing peptide (DSIP) is an endogenous peptide that is constantly present in several different brain regions. Lindane is used as a pesticide and scabicide, but it also induces seizures refractory to conventional antiepileptics. The aim of this paper was to determine whether DSIP modulates lindane-induced seizures in rats in a behavioral and electroencephalographic (EEG) study. DSIP (1 mg/kg, i.p.) or dimethyl-sulfoxide (DMSO, 0.5 ml/kg, intraperitoneally (i.p.)) were injected 30 min before lindane (8 mg/kg, i.p.) to adult male rats with previously implanted electrodes for EEG registration. During the following 30 min, the EEG was registered, and the following behavioral characteristics of seizures were observed: incidence, latency and intensity. A descriptive scale with grades from 0 to 4 provided an estimate of seizure intensity. In the EEG, the number and duration of ictal periods were analyzed using NeuroSciLaBG (Belgrade, Serbia) software. The lethality rate was also analyzed. DSIP-treated animals showed significantly modified characteristics of lindane-induced seizures when compared to the group without DSIP pretreatment (i.e. a reduced seizure intensity and a prolonged seizure latency period). However, no significant effects of DSIP on seizure incidence and lindane-induced lethality were observed. EEG analyses showed a significantly decreased number of lindane-induced EEG ictal periods in DSIP-treated animals, but with unaltered duration. These results show that DSIP favorably modulates lindane-induced seizures in rats, showing a potential to be an adjuvant component of antiepileptic treatment strategy for refractory seizures. https://doi.org/10.2298/ABS180109017H Received: January 9, 2018; Revised: February 7, 2018; Accepted: March 30, 2018; Published online: April 19, 2018 How to cite this article: Hrncic D, Grubac Ž, Sutulovic N, Rasic-Markovic A, Ademovic A, Stanojlovic O. Modulatory effects of delta sleep-inducing peptide in a lindane model of generalized seizures. Arch Biol Sci. 2018;70(3):…