Neonatal co-lesion
by DSP-4 and 5,7-DHT produces adulthood
behavioral sensitization to dopamine D(2)
receptor agonists
Nowak P, Nitka D, Kwiecinski A, Josko J,
Drab J, Pojda-Wilczek D, Kasperski J, Kostrzewa
RM, Brus R.
Department of Pharmacology,
Medical University of Silesia, Zabrze,
Poland
To assess the possible modulatory effects of
noradrenergic and serotoninergic neurons on
dopaminergic neuronal activity, the
noradrenergic and serotoninergic neurotoxins
DSP-4
N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine
(50.0 mg/kg, sc) and 5,7-dihydroxytryptamine
(5,7-DHT) (37.5 mug icv, half in each lateral
ventricle), respectively, were administered
toWistar rats on the first and third days of
postnatal ontogeny, and dopamine (DA)
agonist-induced behaviors were assessed in
adulthood.
At eight weeks, using an HPLC/ED technique,
DSP-4 treatment was associated with a reduction
in NE content of the corpus striatum (> 60%),
hippocampus (95%), and frontal cortex (>
85%), while 5,7-DHT was associated with an
80-90% serotonin reduction in the same brain
regions. DA content was unaltered in the
striatum and the cortex. In the group lesioned
with both DSP-4 and 5,7-DHT, quinpirole-induced
(DA D(2) agonist) yawning,
7-hydroxy-DPAT-induced (DA D(3) agonist)
yawning, and apomorphine-induced (non-selective
DA agonist) stereotypies were enhanced. However,
SKF 38393-induced (DA D(1) agonist) oral
activity was reduced in the DSP-4 + 5,7-DHT
group.
These findings demonstrate that DA D(2)- and
D(3)-agonist-induced behaviors are enhanced
while DA D(1)-agonist-induced behaviors are
suppressed in adult rats in which brain
noradrenergic and serotoninergic innervation of
the brain has largely been destroyed. This study
indicates that noradrenergic and serotoninergic
neurons have a great impact on the development
of DA receptor reactivity (sensitivity).
