E. Acquas et G. Di Chiara, Dopamine D-1 receptor-mediated control of striatal acetylcholine release by endogenous dopamine, EUR J PHARM, 383(2), 1999, pp. 121-127
The role of dopamine D-1 and D-2 receptors in the control of acetylcholine
release in the dorsal striatum by endogenous dopamine was investigated by m
onitoring with microdialysis the effect of the separate or combined adminis
tration of the dopamine D-1 receptor antagonist, SCH 39166 {(-)-trans-6,7,7
a,8,9,13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-naphto-[2,1,b]-
azepine hydrochloride} (50 mu g/kg subcutaneous (s.c.)), of the dopamine D-
2/D-3 receptor agonist, quinpirole (trans-(-)-4aR,4a,5,6,7,8,8a,9-octohydro
-5-propyl-1H-pyrazolo-(3,4-g)-quinoline hydrochloride) (5 and 10 mu g/kg s.
c.), and of the D-3 receptor selective agonist, PD 128,907 [S(+)-(4aR,10bR)
-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-o
l hydrochloride] (50 mu g/kg s.c.), on in vivo dopamine and acetylcholine r
elease. Microdialysis was performed with a Ringer containing low concentrat
ions (0.01 mu M) of the acetylcholinesterase inhibitor, neostigmine. Quinpi
role(10 mu g/kg s.c.) decreased striatal dopamine and acetylcholine release
. Administration of PD 128,907 (50 mu g/kg) decreased dopamine but failed t
o affect acetylcholine release. SCH 39166 (50 mu g/kg s.c.) stimulated dopa
mine release and reduced acetylcholine release. Pretreatment with quinpirol
e reduced (5 mu g/kg s.c.) or completely prevented (10 mu g/kg s.c.) the st
imulation of dopamine release elicited by SCH 39166 (50 mu g/kg s.c.); on t
he other hand, pretreatment with quinpirole (5 and 10 mu g/kg) potentiated
the reduction of striatal acetylcholine release induced by SCH 39166 (50 mu
g/kg s.c.). Similarly, pretreatment with PD 128,907 (50 mu g/kg) which pre
vented the increase of dopamine release induced by SCH 39166 (50 mu g/kg),
potentiated the reduction of striatal acetylcholine transmission elicited b
y SCH 39166. Thus, pretreatment with low doses of quinpirole or PD 128,907
influences in opposite manner the effect of SCH 39166 on striatal dopamine
and acetylcholine release, counteracting the increase of dopamine release a
nd potentiating the decrease in acetylcholine release. These results provid
e further evidence for the existence of a tonic stimulatory input of endoge
nous dopamine on striatal acetylcholine transmission mediated by dopamine D
-1 receptors. (C) 1999 Elsevier Science B.V. All rights reserved.