Mechanisms underlying δ- and μ-opioid receptor agonist-induced increases in extracellular dopamine level in the nucleus accumbens of freely moving rats

Abstract

Abstract:The nucleus accumbens is a terminal area of the mesolimbic dopaminergic system that arises in the ventral tegmental area. Opioids are thought to enhance dopaminergic activity in the nucleus accumbens by activating δ-and μ-opioid receptors in the ventral tegmental area. However, δ-and μ-opioid receptor agonists increase extracellular levels of accumbal dopamine when infused directly into the nucleus accumbens of rats. Therefore, the roles of δ-and μ-opioid receptors in regulation of accumbal dopaminergic neural activity have been analyzed by using δ-and μ-opioid receptor ligands. This review describes the mechanisms underlying the stimulatory effects on accumbal dopamine efflux, which are induced by local administration of δ-and μ-opioid receptor agonists into the nucleus accumbens of freely moving rats. The focus of this article is neurochemical studies that use in vivo microdialysis techniques. Taken together, the in vivo neurochemical evidence from these studies indicates that δ-and μ-opioid receptor agonists increase accumbal dopamine efflux by activating naloxone-sensitive opioid receptors, and by mechanisms independent of naloxone-sensitive opioid receptors, in the nucleus accumbens.

Oral supplementation with ginseng polysaccharide promotes food intake in mice

“…The release of DA from the ventral tegmental area (VTA) plays an important role in the rewarding effect. It has been reported that activation of opioid peptide receptors can promote feeding by palatability (Kelley, Baldo, Pratt, & Will, 2005), and later studies have found that opioid peptide agonists can increase the level of DA in nucleus accumbens (NAc), producing feelings of pleasure and reward (Saigusa, Aono, & Waddington, 2017). The DA reward system is also regulated by hormones and nutrients.…”

Tactile Stimulation in Adult Rats Modulates Dopaminergic Molecular Parameters in the Nucleus accumbens Preventing Amphetamine Relapse

“…In this sense, μ-opioid receptor (MOR) is an important mediator of rewarding properties and additive behavior [ 69 , 70 ] and they are located in the GABAergic interneurons [ 71 ]. NAc is a brain area with considerable MOR density [ 72 ]. Increased MOR resulting from psychostimulant drug administration is related to increased vulnerability to relapse [ 73 ], what was also observed in our AMPH-exposed animals.…”

The role of enkephalinergic systems in substance use disorders

“…Perhaps the most obvious interaction between the two systems is that MOR activation by exogenously administered agonists, such as morphine, stimulate dopamine release in the NAc. Further, KOR activation reduces dopamine release (Escobar et al, 2020), and DOR activation may increase dopamine release to some extent (Saigusa et al, 2017) or have no effect on dopamine (Longoni et al, 1998).…”

“…MOR agonists increase dopamine in the dorsal and ventral striatum (via disinhibition) by activating MORs in the VTA/substantia nigra. MORs do not seem to be located presynaptically on dopamine terminals in the NAc (Svingos et al, 1996;Britt and McGehee, 2008;Saigusa et al, 2017; but see Svingos et al, 1999), but may be present presynaptically in the VP to gate dopamine release arising from the VTA (Mitrovic and Napier, 2002;Root et al, 2015;Clark and Bracci, 2018).…”

“…However, SNC80 did enhance amphetamine-mediated dopamine efflux in the striatum (Bosse et al, 2008) as well as amphetaminemediated locomotor activity (Jutkiewicz et al, 2008) potentially through indirect actions with glutamatergic neurons. The effects of DOR activation on modulating dopaminergic neurotransmission is unclear (for review, see: Saigusa et al, 2017), but overall, enkephalin and opioid receptor activation seem to have some neuromodulatory effects on dopaminergic activity in the reward pathway, most likely through indirect mechanisms.…”