Investigation of the actions of the benzodiazepine antagonists Ro 15-1788 and CGS 8216 using the schedule-controlled behavior of rats.

Ro 15-1788 and CGS 8216 antagonise many of the pharmacological effects of benzodiazepines but both of these compounds have also been shown to exert behavioral effects when administered alone. In the present study the effects of Ro 15-1788 and CGS 8216, alone and in combination with diazepam and with the benzodiazepine receptor ligand zolpidem, were investigated. Diazepam and zolpidem produced dose-related decreases in rates of food-reinforced lever-pressing maintained by a fixed-ratio (FR 10) schedule. CGS 8216 also reduced response rates although Ro 15-1788, at several doses, produced small, but statistically significant, increases in responding. When the diazepam and zolpidem dose-response curves were re-established in the presence of a dose of Ro 15-1788 or CGS 8216 the depressant effects of the higher doses were antagonised. However, neither diazepam nor zolpidem blocked the rate reducing effect of CGS 8216 which may not therefore be due to an action at benzodiazepine receptors.