[Effects of anxiolytic drugs on rewarding and aversive behaviors induced by intracranial stimulation]

Abstract

In considering characteristics of action of anxiolytic drugs and the mechanism of drug action in the brain, it may be necessary to study not only the behavioral pharmacology but also the brain site. In the present study, anxiolytic drugs have been examined in various kinds of behaviors induced by stimulating the brain areas with regard to emotional expression such as reward (pleasure) or aversion in rats. First, the low rate responding on lateral hypothalamic self-stimulation behavior was induced by schedules of low current brain stimulation, variable interval (VI) and differential reinforcement of low rate (DRL). Anxiolytic drugs such as benzodiazepines facilitated these low rate responses. The drug susceptibility was high in the order of the low current stimulation > VI > DRL schedules. Furthermore, it was found by the auto-titration method on intracranial self-stimulation behavior that anxiolytic drugs decreased the threshold of stimulation reward. Second, it was recognized using the decremental lever pressing (DLP) paradigm that anxiolytic drugs increased the threshold of aversive stimulation of mesencephalic dorsal central gray (DCG), and this increasing effect of the drug was antagonized by GABA receptor blockers such as biccuculline. Third, it has been examined whether the conflict situation is established by combining with brain stimulation reward and aversion such as foot-shock or DCG stimulation. As a result, the conflict behavior was established by combining with not only the brain stimulation reward and foot shock aversion, but also the brain stimulation reward and DCG stimulation aversion. Further anxiolytic drugs exhibited the anti-conflict action to both situations. The susceptibility of anxiolytic drugs to the conflict behavior by intracranial reward and aversion was higher than the conventional method based on milk reward and foot shock aversion. Indeed, in the present brain stimulation behavioral study, anxiolytic drugs such as benzodiazepines increased the stimulation threshold in lateral hypothalamic self-stimulation and inhibited the DCG aversive stimulation, i.e. resulting in an anticonflict action of the drugs. Recently we have preliminarily established a new model for evaluating the drug which may facilitate the motivation contributing to result in various behaviors, using the priming stimulation paradigm in intracranial self-stimulation behavior. Diazepam, benzodiazepine, and nomifensine, an dopamine uptake inhibitor, exhibited a delay of the extinction process which included non-reinforcing stimulation and pretrial electric stimulation (priming stimulation) in the self-stimulation behavior. This action may be related to the brain-mechanism of motivation.