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  • Title: Opioid receptor-mediated inhibition of dopamine and acetylcholine release from slices of rat nucleus accumbens, olfactory tubercle and frontal cortex.
    Author: Heijna MH, Padt M, Hogenboom F, Portoghese PS, Mulder AH, Schoffelmeer AN.
    Journal: Eur J Pharmacol; 1990 Jun 08; 181(3):267-78. PubMed ID: 2166675.
    Abstract:
    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 kappa agonist, U 50,488 (1-100 nM), and this inhibition was fully antagonized by the selective kappa antagonist, norbinaltorphimine (nor-BNI). In the frontal cortex, the mu agonist, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, 0.01-1 microM), also inhibited the evoked release of tritium. However, further experiments (including the use of the D2-receptor agonist, LY 171555, and the alpha 2-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 microM) and the delta agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE, 0.01-1 microM). These inhibitory effects were antagonized by 0.1 microM naloxone but not by 3 nM nor-BNI. The irreversible delta ligand, fentanyl isothiocyanate (FIT, 1 microM), 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 kappa 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.
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