Threshold procedures for assessing the impact of agents on brain reward systems

Abstract

Chemical effects on the reinforcing quality of electrical stimulation of the rat brain can be assessed using a variety of methods, most commonly by observing changes in response rates maintained under specific schedules of reinforcement. We present results demonstrating the utility of procedures for assessing the minimum amount of electrical stimulation required to support rat leverpress responding, that is, the brain-stimulation reward (BSR) threshold. In these threshold procedures, each leverpress produced by the rat decreases the duration of the electrical stimulus delivered to the posterior lateral hypothalamus until the rat fails to respond. The stimulus duration is then reset to its initial value and the procedure begins again. The last stimulus duration in a series supporting a response is defined as the stimulus duration (SD) threshold, and the mean SD threshold is determined daily. Stable SD thresholds are achieved within 2 weeks, and this measure is sensitive to agent-induced changes in rats' response to BSR. To illustrate the utility of this approach, data are presented showing that rats' BSR thresholds changed significantly following exposure to triethyltin or carbon monoxide. The results support the view that threshold methods can be used to dissociate agent-induced effects on brain reward systems and BSR quality from changes in performance or effects on other behavioral processes.