Pentobarbital alters the response of cerebrospinal fluid pressure evoked by two provocative tests in rats

The intracerbroventricular (ICV) route of administration is a commonly used pharmacologic procedure in rats. However, little attention is given to changes in cerebrospinal fluid pressure (CSFp) when the ventricular system is perturbed, especially in conscious animals. This communication examined CSFp in pentobarbital-anesthetized rats subjected to two pertubations where CSFp had been previously measured in conscious rats. Pentobarbital treatment resulted in marked, qualitative differences after both protocols. Whereas conscious rats responded to a 10-min ICV infusion (8 microliters/min) by a delayed, secondary increase in CSFp, this effect was completely eliminated (p < 0.001) by pentobarbital. Also, whereas conscious rats could maintain CSFp at normal values during an hour of 45 degrees head-down tilt, pentobarbital-treated rats could not. Anesthetized rats displayed an immediate fall in CSFp to near zero values (p < 0.001), followed by a rapid recovery (p < 0.001) after tilting. Such differences in CSF dynamics raise important issues. For example, what mechanism(s) underlie the changes in CSF dynamics? Also, are these differences in conscious and anesthetized rats potential variables for drug distribution when the ICV route is used?