This study tests the hypothesis that activation of protein kinase C (PKC) i
s a critical step for early recovery from spontaneous nystagmus after unila
teral ablation of the vestibular periphery. Halothane-NO2-O-2-anesthetized
Long-Evans rats received a 5-mu l intracerebroventricular bolus of vehicle
(distilled water, six rats), PKC inhibitor [Iso-H-7 (10 mM, four rats; 50 m
M, five rats) or bisindolemaleimide I(Bis-I, 10 mu M, six rats)], PKG and P
KA inhibitor (A-3, 1 mM, six rats), or the serine-threonine protein kinase
inhibitor H-7 (1 mM, five rats; 10 mM, five rats). Surgical unilateral laby
rinthectomy (UL) was completed within 15 min. Sham control groups showed no
nystagmus. Bis-I and Iso-H-7 significantly retarded the disappearance of s
pontaneous nystagmus quick phases for 8 h after UL (p < 0.05). The effects
of Iso-H-7 were dose-dependent: more nystagmus quick phases (p < 0.05) were
present in the 50 mM than the 10 mM group at 7 and 8 h post-UL. The rats g
iven A-3 showed a delayed retardation of nystagmus loss, which differed sig
nificantly (p < 0.05) from controls at 4-8 h after labyrinthectomy. The num
ber of nystagmus quick phases was significantly greater than controls (p <
0.05) in the 10 mM H-7 group at 4, 5, 6 and 48 h post-UL, but only at 6 and
24 h post-UL in the 1 mM H-7 group. Thus, PKC activation is an important e
arly requirement for vestibular compensation during the acute post-labyrint
hectomy period, while cyclic-nucleotide dependent kinases may be important
in a later time frame. (C) 1999 Elsevier Science B.V. All rights reserved.