CHANGES OF D(1) AND D(2) RECEPTORS IN ADULT-RAT NEOSTRIATUM AFTER NEONATAL DOPAMINE DENERVATION - QUANTITATIVE DATA FROM LIGAND-BINDING, IN-SITU HYBRIDIZATION AND IONTOPHORESIS
F. Radja et al., CHANGES OF D(1) AND D(2) RECEPTORS IN ADULT-RAT NEOSTRIATUM AFTER NEONATAL DOPAMINE DENERVATION - QUANTITATIVE DATA FROM LIGAND-BINDING, IN-SITU HYBRIDIZATION AND IONTOPHORESIS, Neuroscience, 57(3), 1993, pp. 635-648
The specific binding of [H-3]SCH23390 to D1 and of [H-3]raclopride to
D2 dopamine receptors was measured by autoradiography in the rostral a
nd caudal halves of neostriatum and in the substantia nigra of adult r
ats subjected to near total destruction of nigrostriatal dopamine neur
ons by intraventricular 6-hydroxydopamine soon after birth. Three mont
hs after this lesion, [H-3]SCH23390 binding (D1 receptors) was slightl
y but significantly decreased in the rostral neostriatum (22%), but un
changed in its caudal half and in the substantia nigra. In contrast, [
H-3]raclopride binding (D2 receptors) was considerably increased throu
ghout the neostriatum (10-40%), while markedly decreased in the substa
ntia nigra (80%). In the rostral neostriatum, there were no parallel c
hanges in D2 receptor messenger RNA levels, as measured by in situ hyb
ridization on adjacent sections. Caudally, however, slight but signifi
cant increases in D2 messenger RNA could be observed (10-20%). As asse
ssed by quantitative iontophoresis, there was a marked enhancement (63
%) of the inhibitory responsiveness of spontaneously firing units in t
he rostral neostriatum to dopamine and the D, agonist, SKF38393, in ne
onatally lesioned compared to control rats. On the other hand, respons
iveness to PPHT, a potent D2 agonist, appeared to be unchanged. Such o
pposite changes in the number of D1 and D2 binding sites, dissociated
from the expression of D2 receptor messenger RNA and from the sensitiv
ity to dopamine and D1 and D2 agonists, suggested independent adaptati
ons of these various parameters following the neonatal dopamine denerv
ation of neostriatum. They also provided further evidence for mechanis
ms other than the dopamine innervation in the control of the expressio
n of neostriatal D2 receptor messenger RNA during ontogenesis, and emp
hasized that the effects of dopamine and its D1 and D2 agonists in neo
striatum do not depend strictly on the number of D1 and D2 primary lig
and recognition sites.