276 Brain Research, 196 (1980) 276 281

i(5)Elsevier/North-Holland Biomedical Press

Simultaneous demonstration of the activation of presynaptic dopamine

autoreceptors and postsynaptic dopamine receptors in vitro by
N,N -dipropyl-5,6-ADTN

JOHANNES C. STOOF, ALAN S. HORN and ARIE H. MULDER

Departments of Neurology and Pharmacology, Free University Medical Faculty, van der Boeehorststraat
7, 1081 BT Amsterdam and (A. S. H.) Department of Pharmacy, University of Groningen, Antonius
Deusinglaan 2, Groningen (The Netherlands)
(Accepted April 17th, 1980)

Key words: acetylcholine release - - caudate nucleus -- dopamine release -- N,N-dipropyl-5,6-

ADTN -- postsynaptic dopamine receptors -- dopamine autoreceptors

Several lines of evidence indicate that in the neostriatum activation of post-

synaptic dopamine (DA) receptors inhibits the release of acetylcholine (ACh)from
cholinergic interneurones. For instance, it has been reported that neostriatal ACh
levels were increased after pretreatment with the DA receptor agonist apomorphine,
and decreased after pretreatment with neuroleptics such as haloperidol and chlorpro-
mazinen,l°,lL Moreover, using the push-puU cannula technique, Bartholini et al. 2
have shown that apomorphine or L-DOPA inhibit ACh release from cat neostriatum
and that these inhibitory effects are antagonized by neuroleptics. In accordance with
these data we have recently found zl that the depolarization-induced release of radio-
labelled ACh from neostriatal slices was inhibited by various DA receptor agonists,
and that these inhibitory effects were antagonized by haloperidol. It was further
demonstrated that supersensitivity of the DA receptors involved developed following
neonatal treatment with 6-hydroxydopamine. Based on these data we suggested that
ACh release from neostriatal slices provides a functional in vitro parameter to
investigate the activity of drugs on postsynaptic DA receptors 21.
In addition to postsynaptic DA receptors, the existence of DA receptors on
dopaminergic nerve terminals (i.e. auto-receptors) has been proposed. These DA auto-
receptors are thought to regulate DA synthesis and release by a local negative feed-
back mechanism. For instance, DA receptor agonists have been shown to inhibit DA
synthesis from radiolabelled tyrosine in striatal slices or synaptosomal prepara-
tionsS,la, 22. On the other hand, in view of conflicting evidence the existence of DA
auto-receptors, which inhibit transmitter release directly, i.e. not as a result of the inhi-
bition of DA synthesis, is still a matter of controversy. Thus, a number of groups~,16,19
have reported that D A receptor agonists inhibit the release of radiolabelled DA from
striatal slices, while othersX,14, a7 did not observe such an inhibition of DA release.