The use of brain slices in central nervous system pharmacology

Abstract

Brain slice preparations have most frequently been employed to answer questions of a biochemical or physiological nature. Nevertheless, in vitro brain slices also have considerable value as pharmacological tools with which to study the physiological actions of neurotransmitters and drugs on the central nervous system. Several aspects of the slice preparation facilitate this type of analysis. Because drugs can be applied and tested in a relatively quantitative manner, many classical pharmacological techniques (e.g., dose-response curves, tests for competitive vs. noncompetitive antagonism) can be used to examine drug responses. At the simplest level, these techniques facilitate the differentiation of specific (primarily receptor-mediated) and nonspecific actions of drugs and neurotransmitters. As another consequence, the electrophysiological actions of drugs can be directly compared to their biochemical effects in vitro (receptor binding, activation or inhibition of adenylate cyclase, etc.). Ultimately, parallel studies of this type can be used to establish mechanisms of action for various neurotransmitters, particularly those that may employ biochemical substrates as second messengers. In this paper we describe in general terms many of the advantages of the slice preparation as a neuropharmacological tool. Some of the criteria useful in determining the involvement of various receptors in drug-induced changes in electrophysiological responses are discussed in detail. Finally, the responses of hippocampal slices to various adrenergic agents are used to illustrate the way in which various features of this preparation can be exploited pharmacologically. The results of these experiments constitute a significant advance in terms of our understanding of the neuropharmacology of catecholamine responses in this brain region.