Xenobiotics in the limbic system--affecting brain's network function

Xenobiotic compounds enter the brain through nutrition, environmentals, and drugs. In order to maintain intrinsic homeostasis, the brain has to adapt to xenobiotic influx. Among others, steroid hormones appear as crucial mediators in this process. However, especially in the therapy of neurological diseases or brain tumors, long-term application of neuroactive drugs is advised. Several clinically important malignancies based on hormonal dysbalance rise up after treatment with neuroactive drugs, for example, sexual and mental disorders or severe cognitive changes. A drug-hormone cross talk proceeding over drug-mediated cytochrome P450 induction predominantly in the limbic system and the blood-brain barrier, consequently altered steroid hormone metabolism, and P450-mediated change of steroid hormone receptor expression and signaling may serve as an explanation for such disorders. Especially, the interplay between the expression of AR and P450 at the blood-brain barrier and in structures of the limbic system is of considerable interest in understanding brain's reaction on xenobiotic treatment. This chapter summarizes present models and concepts on brain's reaction after xenobiotics crossing the blood-brain barrier and invading the limbic system.