C. Heim et al., Progressive degeneration of dopamine system functions after transient cerebral oligemia in rats, BRAIN RES, 851(1-2), 1999, pp. 235-246
A reduction in cerebral blood flow to oligemic levels was achieved in pento
barbital-anesthetized adult rats by clamping both carotid arteries (BCCA) f
or 60 min. To assess the extent to which the animals' dopaminergic system w
as affected over an increasing time span, their spontaneous locomotor activ
ity in an unfamiliar environment and in response to the subcutaneous admini
stration of apomorphine was tested at various times after either BCCA or sh
am operation. Eight to 14 days after the operation, it was possible to obse
rve a diminished locomotor activity in response to apomorphine injection in
BCCA as compared with sham-operated animals, while oral stereotypical beha
vior such as Licking was increased. At 3 months, there was only a subtle de
crease in apomorphine-induced locomotor activity, and stereotypical behavio
r was similar in both groups. At 7 months, the BCCA rats covered shorter di
stances than sham-operated controls during the habituation phase; after apo
morphine injection, more stereotypic movements, such as, e.g., sniffing, we
re observed, and less running. Twelve months after surgery, no further diff
erences could be observed between the two groups during the habituation pha
se, but the injection of apomorphine led to increased stereotypic sniffing
movements, rearing and locomotor activity in BCCA animals to a greater exte
nt than in the controls. At 12 months, sensorimotor disturbances elicited b
y the rota rod test, which were only transiently observed at 11 weeks and 7
months, did not appear any different from the normal age-related motor dec
line of the sham-operated controls. The animals' motor co-ordination in the
chimney test was not significantly disturbed during the time between 7 and
12 months after surgery, At 15 months, nocturnal locomotor activities in B
CCA rats were significantly decreased. In situ hybridization (ISH) histoche
mistry revealed decreased D1 receptor mRNA (D1RmRNA) in striatal neurons 19
months after surgery, while D2 receptor mRNA (D2RmRNA) and the neuronal nu
mber remained the same. The present results show that just as is already kn
own for the immature rat brain, the adult rat brain, too, reacts to a trans
ient decrease in its blood supply by appearance of long-lasting alterations
in function, and that even a single oligemic episode is capable of inducin
g progressive dopaminergic dysfunctions and ultimately the partial loss of
striatal D1RmRNA. (C) 1999 Elsevier Science B.V. All rights reserved.