Stimulation of D2-receptors in rat nucleus accumbens slices inhibits dopamine and acetylcholine release but not cyclic AMP formation.

We compared some functional responses of D1- and D2-receptor stimulation in tissue slices of rat neostriatum with those in slices of the nucleus accumbens. In both brain regions D2-receptor stimulation inhibited the electrically evoked release of radiolabeled dopamine and acetylcholine. In both brain regions D1-receptor stimulation and forskolin increased the cyclic AMP formation. Only in the neostriatum, stimulation of D2-receptors inhibited the formation of cyclic AMP, brought about by forskolin or by D1-receptor stimulation. It is concluded from these experiments that, although functional responses of D2-receptor stimulation can be demonstrated in the nucleus accumbens, D2-receptors in this brain region are apparently uncoupled to adenylate cyclase.

Opioid and D-2 receptor mediated inhibition of forskolin-stimulated cyclic AMP efflux from rat neostriatal slices.

Opioid and D-2 receptor agonists inhibit adenylate cyclase activity in neostriatal slices and homogenates. In the present study we used cyclic AMP efflux from rat neostriatal tissue as a parameter to estimate the effects of these drugs on cyclic AMP formation. Both the mu-opioid receptor agonist morphine and the D-2 dopamine receptor agonist LY 171555 were able to inhibit the forskolin-stimulated cyclic AMP efflux. The effects of morphine and LY 171555 could be reversed by naloxone and sulpiride, respectively. These data indicate that measurements of cyclic AMP efflux from brain slices is an accurate reflection of the effects of receptor stimulation on adenylate cyclase activity.

D2-dopamine receptors regulate the release of [3H]dopamine in rat basal hypothalamus and neurointermediate lobe of the pituitary gland.

Homogenates of the rat basal hypothalamus and the neurointermediate lobe of the pituitary gland contained relatively high levels of dopamine as was estimated by high-performance liquid chromatography (HPLC). The release of [3H]dopamine was studied in these regions and desipramine was used to prevent uptake of [3H]dopamine in noradrenergic nerve terminals. The release of radioactivity could be stimulated electrically and was calcium-dependent. It appeared that the release of radioactivity could be inhibited by drugs stimulating D2-dopamine receptors in both regions. The radioactivity released during electrical stimulation was analysed by cation exchange chromatography and appeared to consist predominantly of [3H]dopamine. It is our conclusion that D2-receptors mediate the inhibition of the release of [3H]dopamine from dopaminergic nerve terminals in the basal hypothalamus and in the neurointermediate lobe.

A comparative study of the dopamine-acetylcholine interaction in telencephalic structures of the rat and of a reptile, the lizard Gekko gecko.

The present study describes an investigation in which the dopamine-acetylcholine interaction in the caudate-putamen of the rat was compared with that in other telencephalic regions of the rat and in telencephalic regions of the Gekko gecko. For the rat these regions included the nucleus accumbens and the entorhinal and parietal cortices, for the gekko the striatum, the dorsal ventricular ridge and the cortex. All investigated brain regions in the rat and the gekko receive dopaminergic projections from the ventral mesencephalon. The cholinergic fibers in the rat caudate-putamen and nucleus accumbens are mainly from intrinsic origin, whereas these fibers in the cortex of the rat and in the striatum and the cortex of the gekko predominantly originate from extrinsic sources. The dopamine-acetylcholine interaction was studied at the level of dopamine receptor-mediated inhibition of the depolarization-induced release of radiolabeled acetylcholine in vitro. It appeared that in the caudate-putamen and nucleus accumbens but not in the entorhinal and parietal cortices of the rat stimulation of D2 receptors inhibits the release of acetylcholine. Although we could demonstrate the presence of D2 dopamine receptor binding in all studied telencephalic structures of the gekko, D2 receptor agonists were unable to inhibit the release of radiolabeled acetylcholine in these regions.

D-2 dopamine-receptors regulate the release of [3H]dopamine in rat cortical regions showing dopamine immunoreactive fibers.

Using an antibody raised against dopamine the occurrence of dopamine-containing fibers was demonstrated in the prefrontal cortex, anterior cingulate cortex, parietal neocortex, piriform cortex and entorhinal cortex. In extracts of these cortical regions significant amounts of dopamine, although approximately a 100-fold less than in the neostriatum or nucleus accumbens, were detected with high performance liquid chromatography. The release of [3H]dopamine from slices of all these cortical regions was studied in vitro in a superfusion system and desipramine was used to prevent the uptake of [3H]dopamine in noradrenergic nerve terminals. It appeared that the electrically evoked release of radioactivity was inhibited by drugs stimulating D-2 dopamine-receptors in all the regions studied. Cation-exchange column chromatography revealed that the radioactivity released consisted predominantly of [3H]dopamine, indicating that D-2 receptors mediate the inhibition of the release of [3H]dopamine from dopaminergic nerve terminals. Likewise, in the neostriatum as well as in the nucleus accumbens D-2 receptor stimulation inhibits the release of [3H]dopamine. Therefore it is our conclusion that D-2 receptors regulate the release of dopamine from dopaminergic neurons originating in the ventral tegmental area as well as in the substantia nigra.