Application of the combined single-cell recording/intracerebral microdialysis method to alcohol research in freely behaving animals.

Intercellular communication in brain is coded in neuronal firing patterns, determined by the interplay of intra- and extracellular molecular systems. It is not clear how ethanol perturbs this molecular interplay in the motivational, emotional, and cognitive neural networks in brain to induce those specific, aberrant, cell-firing patterns that lead to craving for alcohol, excessive alcohol consumption, and impaired cognition. However, resolution of this problem is essential to an understanding of the basic mechanisms of alcohol-related disorders and to develop effective therapies for their treatment. It is difficult to obtain information on the molecular background of cell-firing regulation in brain during behavioral events. We have recently developed a new in vivo method, combined single-cell recording/intracerebral microdialysis in freely behaving animals, which has the ability to extract such information from brain. The principal feature of the technique is that it records the firing of single neurons in discrete brain sites and deliver drugs, alone or in combinations, via microdialysis, into the extracellular environment of the recorded cells, while the experimental animal is behaving freely. Accordingly, the method allows the determination of drug actions on cellular firing within distinct neural circuits during normal and abnormal behaviors. Thus, it can provide insights into the physiological or pathophysiological molecular machinery of the examined cells. The present paper describes this method, demonstrates how administration of ethanol via intrahippocampal microdialysis affects the firing of hippocampal place cells, and discusses the potential of the technique in future alcohol research.