THRESHOLD OF DOPAMINE CONTENT AND D-1 RECEPTOR STIMULATION NECESSARY FOR THE EXPRESSION OF ROTATIONAL BEHAVIOR INDUCED BY D-2 RECEPTOR STIMULATION UNDER NORMO AND SUPERSENSITIVE CONDITIONS
G. Dziewczapolski et al., THRESHOLD OF DOPAMINE CONTENT AND D-1 RECEPTOR STIMULATION NECESSARY FOR THE EXPRESSION OF ROTATIONAL BEHAVIOR INDUCED BY D-2 RECEPTOR STIMULATION UNDER NORMO AND SUPERSENSITIVE CONDITIONS, Naunyn-Schmiedeberg's archives of pharmacology, 355(1), 1997, pp. 30-35
We measured the minimum amount of endogenous dopamine (EDA), necessary
for the expression of rotational behaviour induced by D-2 receptor st
imulation in striatal or medial forebrain bundle (MFB) lesioned rats.
We correlated these results with the minimum dose of D-1 receptor agon
ists needed to substitute EDA in its permissive role for D-2 motor eff
ects to take place. Rats with unilateral quinolinic acid (AQ) striatal
or 6-hydroxydopamine (6-OHDA) MFB lesions were given increasing doses
of the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMP
T) in combination with a fixed dose of the D-2 receptor agonist quinpi
role R-4,4a,5,6,7,8,8a,9-Octahydro-5-pyopyl-1H-pyrazolo (3,4-g)quinoli
ne hydrochloride) and tested for rotational behavior. The animals were
later sacrificed and striata removed; EDA ws measured by high perform
ance liquid chromatography (HPLC). Rotational responses were abolished
by increasing doses of AMPT inducing a stepwise depletion of EDA. EDA
content and rotational behavior to D-2 stimulation showed a high degr
ee of correlation. There was an abrupt reduction in rotational behavio
r at dopamine levels of 50-60% of controls in both animal models. In a
ddition, striatal or MFB lesioned rats which were maximally depleted o
f dopamine by AMPT pretreatment received a fixed dose of quinpirole an
d then challenged with increasing doses of D-1 receptor agonist SKF 38
393 nyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride).
Rotational behavior was restored by SKF 38393 in both animal models i
n dose-dependent fashion. Our results confirm the need for simultaneou
s D-1/D-2 stimulation in the generation of rotational behavior in both
animal models. Moreover, they demonstrate the existence of a threshol
d level of D-1 stimulation necessary to exert its permissive role on D
-2 mediated responses.