THE EFFECTS OF ANTIEPILEPTIC DRUGS ON SPATIAL
LEARNING AND HIPPOCAMPAL PKCγ IN IMMATURE RATS
Wu Y, Wang
L
Department
of Pediatrics,
Peking
University First Hospital, Beijing 100034, China
Objective: To study whether the conventional antiepileptic
drugs have effects on learning and memory of the immature rats and what is
the role of PKCγ activation in this process.
Methods: 21-day-old Wistar Rats
were divided into 5 groups:control, training without drug, training with
phenobarbital (PB) , training with carbamazepine(CBZ) and training with
valproate (VPA). Drugs were
administered intraperitoneally (i.p.) in the rats of training with PB, VPA
and CBZ groups. In control and training without drug group, N.S were
administered. A hippocampal dependent learning task-spatial changing
learning was used in the rats of the latter four groups, which lasted 10
days. The correct responding rate (CRR) were calculated after training in
all groups, meanwhile the PKCγ
expression in the hippocampus were tested by immunocyto-chemical
staining and western blot. And then, the CRR and the PKCγ expression were
compared among different groups.
Results: Correct responding rate
(CRR) of training group was significantly higher than that of PB group, CBZ
group and VPA group (P<0.05). The PKCγ staining density in
hippocampal CA1-2 of training group were significant stronger than that of
control group and PB group, no difference were found among CBZ group, VPA
group and training group. The amount of PKCγ in plasma membrane of
hippocampal neurons in training group is significantly higher(P<0.05)
than control, PB and VPA groups, no difference was found between training
and CBZ group. The amount of PKCγ in cell plasma of hippocampus were no
difference among 5 groups.
Conclusion: Our results showed that
PB, VPA and CBZ all could disturb the rat's spatial learning and memory,
activation level of PKCγ in hippocampal neurons was parellel with spatial learning ability of
the immature rats and decreased in PB and VPA treated rats after training.
These indicated that
interference of PKCγ activation was probably one of the
cellular mechanisms of PB and VPA influencing the learning and memory in
the immature rats.