In the model of schizophrenia, pregnenolone sulfate was administered to mice intraperitoneally at 40 or 60 mg/kg. When administered to rats intracerebroventricularly, 12 nmol but not 192 nmol pregnenolone sulfate enhanced spatial memory performance.

Activity with respect to NMDA and GABA uiion channels was measured using whole cell variant of the patch-clamp technique. Patch electrodes were fabricated with a double pull from thin-wall borosilicate glass microcapillary pipets. Electrode resistance was 5.2 ± 0.12 MOhm (n = 65) when filled with intracellular solution. After formation of a tight seal (typically 1-10 GOhm), capacitative transients were minimized. The patch of membrane under the pipet tip was then ruptured by gentle suction, to obtain the whole-cell configuration. Drug solutions were applied to single neurons by pressure ejection (15 psi) from seven-barrel pipets. Under these conditions, the drug solution in the pressure pipet rapidly and effectively replaces the solution surrounding the target neuron, with <10% dilution. In all experiments, neurons received a 10-sec prepulse of either external buffer or drug solution, followed by a 10-sec application of agonist, followed by a 10-20-sec pulse of external buffer solution.