Opioid receptor-mediated inhibition of 3H-dopamine and 14C-acetylcholine release from rat nucleus accumbens slices

Abstract

The release of 14C-ACh from rat nucleus accumbens slices, induced by 15 mM [K+], was inhibited by the mu- and delta-opioid agonists DAMGO and DPDPE, respectively, whereas only the kappa agonist U50,488 reduced the release of 3H-DA. The opioid receptors involved appear to be localized on nerve terminals, since blockade of action potential propagation by 1 microM TTX did not diminish the inhibitory effects of DAMGO, DPDPE or U50,488. Enhancement of the potassium concentration in the superfusion medium to 56 mM with simultaneous reduction of the Ca2+ concentration from 1.2 mM to 0.12 mM induced a release similar to that caused by 15 mM K+ and 1.2 mM Ca+. Under this conditions, the inhibitory effects of both DAMGO and DPDPE on stimulated 14C-ACh release were reduced, whereas the inhibition of evoked 3H-DA release caused by U50,488 was not affected. Activation of mu- as well as delta-opioid receptors by DAMGO and DPDPE, respectively, inhibited forskolin-stimulated adenylate cyclase activity. However, increasing the intracellular cAMP levels with 0.3 mM 8-bromo-cAMP affected neither the depolarization-induced release of 14C-ACh or 3H-DA from accumbens slices nor the inhibitory effects of opioid receptor activation thereon. The results indicate that the mechanism by which functional mu and delta receptors presynaptically inhibit the depolarization-induced 14C-ACh release from nucleus accumbens slices is likely to involve an increase of potassium channel conductance. In contrast, activation of kappa-opioid receptors, which inhibits depolarization-evoked 3H-DA release, apparently does not result in a hyperpolarization of (dopaminergic) nerve terminals. In none of these inhibitory effects presynaptic adenylate cyclase appears to be involved.

Presynaptic Opioid and Nicotinic Receptor Modulation of Dopamine Overflow in the Nucleus Accumbens

“…In light of these observations, we were interested in assessing the effects of -opioid agonists on evoked DA overflow (Schmidt et al, 2002;Woolley et al, 2007). Both rats and humans find -opioids aversive and in microdialysis studies they inhibit DA levels in the NAc shell in rats (Pfeiffer et al, 1986;Heijna et al, 1992;Ronken et al, 1993;You et al, 1999;Thompson et al, 2000;Walsh et al, 2001).…”

A comparison of detomidine in combination with saline, morphine or methadone in horses submitted to experimental oral stimuli

“…Although dopamine is believed to be the primary neurotransmitter involved in opioidergic pathways, other neurotransmitters have been implicated both directly and indirectly (MAMA et al, 1993). Acetylcholine (ACH), norepinephrine (NE) and gamma amino butyric acid (GABA) involvement have been associated with opioidergic neurotransmission in different regions of the rat brain (AUSTIN; KALIVAS, 1989;HEIJNA et al, 1990). Thus, as the α 2-agonists act in part by modulation of central NE release, in combination with opioids the behavioral excitatory response can be reduced.…”

Ultrastructural Immunocytochemical Localization of μ-Opioid Receptors in Rat Nucleus Accumbens: Extrasynaptic Plasmalemmal Distribution and Association with Leu5-Enkephalin

“…These may include acetylcholine or GABA, both of which are modulated presynaptically by MOR agonists in the NAC and dorsal striatum, respectively (Heijna et al, 1992;Jiang and North, 1992). MOR can also regulate dopamine release (Heijna et al, 1990), at least in part through presynaptic mechanisms (Yuan et al, 1992;Pennartz et al, 1994) and GABA A receptor potentials (Siggins and Zieglgansberger, 1981), both of which have been implicated in the rewarding effects of opiates (Koob, 1992).…”