Self-injection of diazepam in naive rats: effects of dose, schedule and blockade of different receptors

Abstract

The present series of experiments had two main objectives: The first was to determine the conditions under which self-injection of the benzodiazepine diazepam would be optimal; the second was to identify neurochemical substrates which underlie the maintenance of diazepam self-administration. Data from the first experiment indicated that rats maintained on an FI-1 (Fixed Interval of 1 min) schedule of food delivery self-injected significantly more diazepam than rats not maintained on this schedule. Results from the second experiment demonstrated that the benzodiazepine antagonist Ro 15-1788, and the GABA antagonist bicuculline, significantly reduced diazepam self-administration, but the opiate antagonist naloxone was without effect. Data from the third experiment showed that the dopamine antagonist haloperidol also significantly reduced the rate of diazepam self-injection. Thus, these findings indicate that the acquisition of diazepam self-injection occurs under an FI-1 schedule of food delivery, which has been shown to be middly stressful, while its maintenance depends upon the functional integrity of benzodiazepine and GABA receptors and upon the activity of dopaminergic pathways.