The modulation of the electrically evoked release of [3H]dopamine (DA) and [14C]acetylcholine (ACh) by opioid receptor activation was examined in superfused slices from rat nucleus accumbens, olfactory tubercle, and frontal cortex. In all brain areas examined, [3H]DA release was inhibited by the κ agonists, U 50,488 (1-100 nM), and this inhibition was fully antagonized by the selective κ antagonist, norbinaltorphimine (nor-BNI). In the frontal cortex, the μ agonist, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, 0.01-1 μM), also inhibited the evoked release of tritium. However, further experiments (including the use of the D2-receptor agonist, LY 171555, and the α2-adrenoceptor agonist, oxymetazoline) suggest strongly that in the frontal cortex DAGO only inhibits the release of [3H]catecholamine from noradrenergic nerve terminals, despite the use of desimipramine to prevent the uptake of [3H]DA into these terminals. [14C]ACh release from both the nucleus accumbens and olfactory tubercle, but not from the frontal cortex, was inhibited by DAGO (0.01-1 μM) and the δ agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE, 0.01-1 μM). These inhibitory effects were antagonized by 0.1 μM naloxone but not by 3 nM nor-BNI. The irreversible δ ligand, fentanyl isothiocyanate (FIT, 1 μM), only antagonized the inhibition caused by DPDPE. The results indicate that the inhibitory effects of opioids on the in vitro release of DA from dopaminergic nerve fibres arising from the substantia nigra and the ventral tegmental area are mediated by presynaptic κ receptors only. In those regions where ACh release is modulated by opioids, the type of opioid receptor involved may depend on the type of neuron, i.e. interneuron or afferent neuron.
Bibliographical noteFunding Information:
The authors thank H. Nordsiek for preparing the figures. This work was supported by Grant 900-549-083 from the Foundation for Medical Research, MEDIGON-NWO, The Hague, The Netherlands and by a Senior Fellowship of the Royal Academy of Sciences and Arts awarded to Dr. A.N.M. Schoffelmeer.
- Acetylcholine release
- Brain slices (rat)
- Dopamine release
- Limbic brain areas
- Opioid receptor subtypes