Diazepam alters brain-stimulation reward thresholds in seizure-prone sites

Abstract

Studies of the effect of diazepam and related compounds on the rewarding properties of brain stimulation as measured by response rates have not yielded clear results, with self-stimulation performance reported to be potentiated, diminished, or unchanged following drug administration. In this study, the effect of two doses of diazepam (2.5 and 5.0 mg/kg) and its vehicle on self-stimulation thresholds was examined in eight rats with electrode placements scattered along a 4 mm length of the medial forebrain bundle. Stimulation of the lateral preoptic area and the anterior and mid-lateral hypothalamus produced overt seizures. Rate-period curves were generated for a wide range of currents and the resulting period-current trade-off functions were compared across doses. In seizure-prone sites upward shifts in period threshold were observed after 2.5 mg/kg of diazepam with little additional increases incurred by the 5.0 mg/kg dose. The majority of non-seizure sites showed no effects of diazepam upon period threshold. The results suggest that diazepam alters brain-stimulation reward thresholds by suppressing competing seizure activity.