The use of a remote-controlled minivalve, carried by freely moving animals on their head, to achieve instant pharmacological effects in intracerebral drug-perfusion studies.

摘要

Intracerebral drug-perfusion studies in animals can be very efficiently performed with the 'reverse-dialysis' procedure. In this procedure, drugs are delivered into the brain via an intracerebrally implanted microdialysis probe. Traditionally, in reverse-dialysis studies the flow of control and drug solutions in the microdialysis site is alternated by large and heavy valves placed far from the experimental animal. In this arrangement, the drugs travel from the fluid-alternating device for a long (20--60 min) period before reaching the brain. This can obscure the onset of drug action, makes it difficult to deliver drugs into the extracellular space during short-lasting behavioral episodes, and considerably limits the number of drug solutions that can be perfused within an experimental session. This report describes the use of a miniature (15 mm long and 8 mm diameter), lightweight (1.4 g) minivalve (patent pending) for combined neuronal recording--intracerebral microdialysis studies in freely moving rats. The device is activated remotely and carried by the animals on their head. This allows the experimenter to alternate the control and drug solutions in the intracerebral recording/dialysis site rapidly and to detect the drug-induced neuronal firing pattern changes instantly, without interfering with the animal's behavior. It is demonstrated that with this novel device the onset of drug actions on hippocampal neurons can be clearly defined and that these actions occur within 2 min after minivalve activation. Furthermore, it is demonstrated that the minivalve allows one to test a large number of drug solutions, successively, within the same experimental session. The described protocol offers a high-throughput method for testing the neuron-specific pharmacological effects of intracerebrally perfused drugs during various behaviors.