Effects of chlordiazepoxide on single-unit activity in the septal region of the freely moving rat: aversive vs. non-aversive contexts

Abstract

Evidence suggests that stimuli that have the property of inhibiting fear in a Pavlovian fear conditioning paradigm increase cellular activity in the lateral septum, a result consistent with the idea that the lateral septum is actively involved in the inhibition of fear. The experiments reported here were designed to determine if an anxiolytic drug with fear-inhibiting properties would also increase neuronal activity in the lateral septum in a manner that might relate to its mechanism of action as an anxiolytic. An experiment was performed to compare the effects of the benzodiazepine anxiolytic chlordiazepoxide (CDP) upon single-unit activity in the septal region of the rat brain during Pavlovian aversive conditioning with the effects of CDP in a non-aversive context. During Pavlovian conditioning there was a decrease in unit activity in the more lateral regions of the septum, the dorsolateral and ventrolateral nuclei, when a stimulus signaling footshock (CS+) was presented. This conditioned suppression of unit activity was blocked by an intraperitoneal injection of CDP. Additionally, CDP increased baseline unit activity in these regions in the absence of conditioned stimuli. In the more medial regions of the septum, the intermediate lateral septum, we observed few consistent changes either to the conditioned stimuli or to the drug. In a non-aversive context CDP had either no effect at low to moderate doses, or a suppressant effect at a higher dose. The results support a fear-relief hypothesis of lateral septal functioning and suggest the lateral septum as a possible site for the anxiolytic action of benzodiazepines.