Introduction

Transport across the blood–brain barrier (BBB) in vivo can be studied by two different experimental strategies. An indirect approach is to measure brain extraction of a compound from blood (or other media) after passage through the brain capillaries, e.g. by the carotid artery single injection technique. A direct means is measuring the concentration of the compound in the brain itself, either after tissue homogenization or by quantitative autoradiography. More sophisticated and noninvasive techniques are PET and NMR. These techniques are however expensive and require specialized equipment and expertise. Another quite appropriate technique is intracerebral microdialysis, which is relatively simple to apply and comparably inexpensive. It allows for the continuous monitoring of levels of compounds within discrete brain regions of a single animal (Ungerstedt, 1984). In recent years the in vivo microdialysis technique has been widely used for a variety of applications. It has been used for pharmacological (Jacobson et al., 1985), physiological (Benveniste et al., 1984), and behavioral studies (Gerozissis et al., 1995) to monitor and analyze endogenous compounds such as neurotransmitters, or exogenous compounds. The technique can also be used for the determination of transport of compounds across the BBB (Allen et al., 1992; De Lange et al., 1994, 1995a-d).