Cellular Sites for Dynorphin Activation of κ-Opioid Receptors in the Rat Nucleus Accumbens Shell

Abstract

The nucleus accumbens (Acb) is prominently involved in the aversive behavioral aspects of kappa-opioid receptor (KOR) agonists, including its endogenous ligand dynorphin (Dyn). We examined the ultrastructural immunoperoxidase localization of KOR and immunogold labeling of Dyn to determine the major cellular sites for KOR activation in this region. Of 851 KOR-labeled structures sampled from a total area of 10,457 microm2, 63% were small axons and morphologically heterogenous axon terminals, 31% of which apposed Dyn-labeled terminals or also contained Dyn. Sixty-eight percent of the KOR-containing axon terminals formed punctate-symmetric or appositional contacts with unlabeled dendrites and spines, many of which received convergent input from terminals that formed asymmetric synapses. Excitatory-type terminals that formed asymmetric synapses with dendritic spines comprised 21% of the KOR-immunoreactive profiles. Dendritic spines within the neuropil were the major nonaxonal structures that contained KOR immunoreactivity. These spines also received excitatory-type synapses from unlabeled terminals and were apposed by Dyn-containing terminals. These results provide ultrastructural evidence that in the Acb shell (AcbSh), KOR agonists play a primary role in regulating the presynaptic release of Dyn and other neuromodulators that influence the output of spiny neurons via changes in the presynaptic release of or the postsynaptic responses to excitatory amino acids. The cellular distribution of KOR complements those described previously for the reward-associated mu- and delta-opioid receptors in the Acb shell.

Exposure to the Selective κ-Opioid Receptor Agonist Salvinorin A Modulates the Behavioral and Molecular Effects of Cocaine in Rats

“…In the dorsal striatum and NAc, KORs inhibit neuronal activity and neurotransmitter release and are primarily located on presynaptic dopaminergic, GABAergic, and glutamatergic afferents, although there is some evidence for localization on medium spiny output neurons (Arvidsson et al, 1995;Svingos et al, 1999;Meshul and McGinty, 2000;Hjelmstad and Fields, 2003). Acute administration of SalvA decreases extracellular concentrations of DA in the dorsal striatum (Zhang et al, 2005) and NAc .…”

Corticotropin-Releasing Factor (CRF)-Induced Disruption of Attention in Rats Is Blocked by the κ-Opioid Receptor Antagonist JDTic

“…Likewise, depletion of DA from the striatum increases both response latencies and omissions (Cole and Robbins, 1989;Baunez and Robbins, 1999), a pattern of effects similar to that which we observed after CRF administration. CRF stimulates dynorphin release (Nikolarakis et al, 1986;Song and Takemori, 1992), which can in turn inhibit DA release via KOR activation at terminals of midbrain DA neurons (Donzanti et al, 1992;Svingos et al, 1999), creating a hypo-dopaminergic state. Additionally, there is evidence that the DRN sends direct projections to the striatum that regulates DA release: activation of 5HT receptors in the striatum increases extracellular concentrations of DA (Benloucif and Galloway, 1991;Benloucif et al, 1993), whereas CRF reduces 5HT release in the striatum (Price et al, 1998), raising the possibility that CRF-induced decreases in 5HT may reduce DA activity in this region.…”

Expression of Amphetamine-Induced Behavioral Sensitization after Short- and Long-Term Withdrawal Periods: Participation of μ- and δ-Opioid Receptors

“…Anatomical and neurochemical evidence support the interaction between the opioidergic and dopaminergic systems within the motive circuit (Di Chiara and Imperato, 1988;Devine et al, 1993;Churchill and Kalivas, 1996;Feigenbaum and Howard, 1997;Svingos et al, 1996Svingos et al, , 1998Svingos et al, , 1999Svingos et al, , 2001Garzon and Pickel, 2001). In addition, in several different animal models of drug reinforcement, opioid receptor antagonists have been shown to attenuate the rewarding effects of psychostimulants (Menkens et al, 1992;Sala et al, 1995;Kuzmin et al, 1997).…”