Electroencephalographic changes after short-term exposure to agonists of benzodiazepine receptors in the rat

Abstract

Naive rats receiving IV diazepam (10 mg/kg), flunitrazepam (2.5 mg/kg) and clonazepam (2 mg/kg) show electroencephalographic (EEG) changes consisting of lengthening of the spindle bursts (7–12 Hz; 200–300 μV) and appearance of 15–30 Hz waves (β-like activity). These EEG manifestations are associated with signs of behavioral sedation (crouched, eyes open and myorelaxation) and stimulation (gnawing, running, ear twitches and sometimes wet-dog shakes), respectively. Bursts of 2–4 Hz waves can be occasionally observed associated with either marked sedation (lying down, eyes closed and presence of righting reflex) or sleep (stretched in the side with absence of rightning reflex). Measurements of the periods spent by the animals in the two EEG patterns within the first hour after intravenous injection show the large preponderance of the spindle bursts over the β-like activity. After the triazolopyridazine Cl 218,872 (10 mg/kg) the β-like activity is almost absent, and in no case loss of the righting reflex can be observed. These agonists of BDZ receptors have been injected at the above reported doses for 5 days, once-a-day. At the 5th day, animals receiving diazepam exhibit a preponderace of the EEG and behavioral activation within the first hour after injection. Rats receiving flunitrazepam show a significant increase of the periods of stimulation and a slight decrease of the periods of sedation. These phenomena of “habituation” are absent in animals treated with clonazepam and Cl 218,872.