PERSISTENT HYPERACTIVITY FOLLOWING A SINGLE INTRACEREBROVENTRICULAR DOSE OF OUABAIN

Intracerebroventricular (ICV) administration of ouabain has been shown to alter motor activity in the rat. It has been purported that this m ay model the behavioral abnormalities of human manic-depressive (bipol ar) illness. Since manic-depression is a recurrent condition, we elect ed to investigate the effects of the multiple administration of ICV ou abain. Male Sprague-Dawley rats were allowed to acclimate to the anima l facility for 7-10 days after which time ICV cannulae were placed. An imals received two ICV injections of either ouabain (10(-3) M) or arti ficial cerebrospinal fluid (aCSF) 9 days apart, so that 6 rats receive d aCSF-aCSF, 6 received ouabain-aCSF, and 6 received ouabain-ouabain. Behavioral activity was evaluated in an open held (86 x 86 cm subdivid ed into sixteen 21.5 x 21.5-cm squares) for 20 min at baseline and imm ediately following each ICV injection. After the last behavioral test, the animals were killed, and the brains were rapidly harvested and di ssected over ice. Specific ouabain binding and sodium pump activity we re determined. A single dose of ouabain produced a marked increase (29 7.0%, p = 0.002) in open field activity compared to both baseline beha vior and to aCSF injected animals. The effects of ouabain appeared to last for 9 days. A second ICV injection-of either ouabain (136.5 +/- 6 0.4 SEM) or aCSF (108.0%, p < 0.01) had no effect on the activity leve l which was intermediate between the initial ouabain hyperactivity and the baseline level. Nine days after ouabain administration, hippocamp al ouabain binding was increased relative to the control group (5477 /- 485.7 vs. 3579 +/- 518.6, p < 0.05) and sodium pump activity was re latively lower (2293.8 +/- 265.5 vs. 3174.2 +/- 410.5, p < 0.05). (C) 1998 Elsevier Science Inc.