Audiogenic seizures (AGS) in genetically
epilepsy-prone rats (GEPR) of the moderateseizure
substrain (GEPR-3s) were investigated
to determine whether norepinephrine (NE)
depletion induced by 6-hydroxydopalnine (6-OHDA)
microinfusion into the locus coeruleus
(LC) could alter the efficacy of intraventricular
NE tissue grafts in promoting reductions in
seizure severity in AGS. GEPR-3s were
stereotaxically infused with 6-OHDA
(4μg/side/rat), or vehicle into the region of the
LC. Following 6-OHDA treatment all animals
were subjected to 3 AGS tests. GEPR-3s seizure
severities were increased in 39.5% of the
animals after microinfusion of 6-OHDA into the
region of the LC. Following the third AGS test,
each rat was stereotaxicaily implanted with 17
gestational day rat fetal tissue obtained from the
dorsal pons and containing the primordia of the
LC or with tissue obtained from the neocortex
or were sham-grafted. Subsequent to grafting,
rats were subjected to 3 additional AGS tests.
53% (10/19) of 6-OHDA treated GEPRs showed
a significant reduction in seizure severity
following transplantation of fetal LC tissue. In
contrast, only 20% (1/5) of GEPRs infused with
saline rather than 6-OHDA showed, a reduction
of seizure severity following fetal LC
transplantation. NE content in the cortex and
pons/medulla was decreased by 78% and 46%
respectively following 6-OHDA microinfusion
into the LC. Prominent grafts with numerous
TH positive neurons and neurites were present
within the third ventricle of grafted animals,
while cortex grafts contained no TH
immunostained structures. These findings
suggest that the efficacy of fetal LC tissue to
promote reductions in seizure severity in GEPRs
is increased following depletion of central NE by
microinfusion of 6-OHDA.