scholarly journals Kappa-opioid receptor-dependent changes in dopamine and affective behavior occur differentially across the nucleus accumbens shell rostro-caudal axis

2020 ◽  
Author(s):  
Breanne E. Pirino ◽  
Mary B. Spodnick ◽  
Andrew T. Gargiulo ◽  
Genevieve R. Curtis ◽  
Jessica R. Barson ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Opioid Receptor ◽  
Dopamine Release ◽  
Neural Circuit ◽  
Ex Vivo ◽  
Kappa Opioid Receptor ◽  
Affective Behavior ◽  
Kappa Opioid ◽  
Affective Behaviors ◽  
The Impact

ABSTRACTNeural circuit engagement within the nucleus accumbens (NAc) shell is implicated in the regulation of both negative and positive affect. Classically, the dynorphin/kappa opioid receptor (KOR) system in the NAc was believed to promote dysphoric behavior, while dopamine was viewed as interacting with reward behavior, and KOR activation was known to inhibit dopamine release. Recently, however, both the KOR and dopamine systems have, separately, been shown to have differential effects across the rostro-caudal axis of the NAc shell on hedonic responses. Whether or not this is due to interactions between KORs and dopamine, and if it extends to other affective behaviors, remains to be determined. In this study, we examined in rats the relationship between the KOR and dopamine systems in both the rostral and caudal NAc shell using ex vivo fast scan cyclic voltammetry and the impact of KOR activation on affective behavior using approach-avoidance assays. We report here that activation of KORs in the caudal NAc shell significantly inhibits dopamine release, stimulates novelty-induced rearing behavior, increases avoidance behavior, and reduces locomotor activity. In contrast, activation of KORs in the rostral NAc shell inhibits dopamine release to a lesser extent and instead increases approach behavior. Taken together, these results indicate that there is heterogeneity across the rostro-caudal axis of the NAc shell in the effects of KOR stimulation on affective behaviors, and they suggest that this might be due to differences in KOR control over dopamine release.

scholarly journals Relative Timing Between Kappa Opioid Receptor Activation and Cocaine Determines the Impact on Reward and Dopamine Release

2015 ◽  
Vol 41 (4) ◽  
pp. 989-1002 ◽  
Author(s):  
Elena H Chartoff ◽  
Shayla R Ebner ◽  
Angela Sparrow ◽  
David Potter ◽  
Phillip M Baker ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Dopamine Release ◽  
Receptor Activation ◽  
Kappa Opioid Receptor ◽  
Relative Timing ◽  
Kappa Opioid ◽  
The Impact

scholarly journals Adolescent intermittent ethanol exposure effects on kappa opioid receptor mediated dopamine transmission: Sex and age of exposure matter

2020 ◽  
Author(s):  
Mary B. Spodnick ◽  
Raymond T. Amirault ◽  
Trevor T. Towner ◽  
Elena I. Varlinskaya ◽  
Linda P. Spear ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Dopamine Release ◽  
Ethanol Exposure ◽  
Kappa Opioid Receptor ◽  
Female Rats ◽  
Male Rats ◽  
Kappa Opioid ◽  
Male And Female Rats ◽  
Dopamine Transmission ◽  
The Impact

ABSTRACTUnderage alcohol drinking increases the risk of developing alcohol use disorder (AUD). In rodents, adolescent ethanol exposure augments ethanol consumption and anxiety-like behavior while reducing social interaction. However, the underlying mechanisms driving these adaptations are not understood. The dopamine and kappa opioid receptor (KOR) systems in the nucleus accumbens (NAc) are implicated in affective disorders and AUD, with studies showing augmented KOR function and reduced dopamine transmission in ethanol-dependent adult animals. Thus, this study, we examined the impact of adolescent intermittent ethanol (AIE) exposure on dopamine transmission and KOR function. Rats were exposed to water or ethanol (4 g/kg, intragastrically) every-other-day during early (PD25–45) or late (PD45–65) adolescence. While AIE exposure during early-mid adolescence (early AIE) did not alter dopamine release in male and female rats, AIE exposure during late adolescence (late AIE) resulted in greater dopamine release in males and lower dopamine release in females. To determine the impact of AIE exposure on KOR function, we bath applied cumulative concentrations of KOR agonist, U50,488 (0.01–1.0 μM), and measured its effect on dopamine release. Early AIE exposure potentiated KOR-mediated inhibition of dopamine release in female rats, while late AIE exposure attenuated this effect in male rats. Together these data suggest that AIE-exposure impact on neural processes is dependent on sex and exposure timing. These differences likely arise from differential developmental timing in males and females. This is the first study to show changes in KOR function following AIE exposure.

scholarly journals Adolescent Intermittent Ethanol Exposure Effects on Kappa Opioid Receptor Mediated Dopamine Transmission: Sex and Age of Exposure Matter

2020 ◽  
Vol 10 (8) ◽  
pp. 472
Author(s):  
Mary B. Spodnick ◽  
Raymond T. Amirault ◽  
Trevor T. Towner ◽  
Elena I. Varlinskaya ◽  
Linda P. Spear ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Dopamine Release ◽  
Ethanol Exposure ◽  
Kappa Opioid Receptor ◽  
Female Rats ◽  
Kappa Opioid ◽  
Male And Female Rats ◽  
Dopamine Transmission ◽  
Underlying Mechanisms ◽  
The Impact

Underage alcohol drinking increases the risk of developing alcohol use disorder (AUD). In rodents, adolescent ethanol exposure augments ethanol consumption and anxiety-like behavior while reducing social interaction. However, the underlying mechanisms driving these adaptations are unclear. The dopamine and kappa opioid receptor (KOR) systems in the nucleus accumbens (NAc) are implicated in affective disorders, including AUD, with studies showing augmented KOR function and reduced dopamine transmission in ethanol-dependent adult animals. Thus, here we examine the impact of adolescent intermittent ethanol (AIE) exposure on dopamine transmission and KOR function in the NAc. Rats were exposed to water or ethanol (4 g/kg, intragastrically) every other day during early (postnatal day (PD) 25–45) or late (PD 45–65) adolescence. While AIE exposure during early adolescence (early-AIE) did not alter dopamine release in male and female rats, AIE exposure during late adolescence (late-AIE) resulted in greater dopamine release in males and lower dopamine release in females. To determine the impact of AIE on KOR function, we measured the effect of KOR activation using U50,488 (0.01–1.00 µM) on dopamine release. Early-AIE exposure potentiated KOR-mediated inhibition of dopamine release in females, while late-AIE exposure attenuated this effect in males. Interestingly, no differences in KOR function were observed in early-AIE exposed males and late-AIE exposed females. Together, these data suggest that AIE exposure impact on neural processes is dependent on sex and exposure timing. These differences likely arise from differential developmental timing in males and females. This is the first study to show changes in KOR function following AIE exposure.

scholarly journals Effects of agonists with mixed efficacy profiles at the mu and kappa opioid receptor on amphetamine‐mediated dopamine release

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Kelly E Bosse ◽  
Faye A Bradbury ◽  
Emily M Jutkiewicz ◽  
Steve M Husbands ◽  
Margaret E Gnegy ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Dopamine Release ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Mixed Efficacy

Neurotensin and Dynorphin Bi-Directionally Modulates CeA Inhibition of oval BNST Neurons in Male Mice

2018 ◽  
Author(s):  
CP Normandeau ◽  
ML Torruella Suárez ◽  
P Sarret ◽  
ZA McElligott ◽  
EC Dumont
Keyword(s):  
Opioid Receptor ◽  
Neural Circuit ◽  
Brain Slices ◽  
Kappa Opioid Receptor ◽  
Male Mice ◽  
Central Amygdala ◽  
Kappa Opioid ◽  
Brain Circuit ◽  
Circuit Function ◽  
The Way

AbstractNeuropeptides are often co-expressed in neurons but their neurophysiological effects are commonly studied individually. Multiple neuropeptides may therefore be simultaneously released to coordinate proper neural circuit function. Here, we triggered the release of endogenous neuropeptides in brain slices from male mice to better understand the modulation of central amygdala (CeA) inhibitory inputs onto oval (ov) BNST neurons. We found that locally-released neurotensin (NT) and dynorphin (Dyn) antagonistically regulated CeA inhibitory inputs onto ovBNST neurons. NT and Dyn respectively increased and decreased CeA-to-ovBNST inhibitory inputs through NT receptor 1 (NTR1) and kappa opioid receptor (KOR). Additionally, NT and Dyn mRNAs were highly co-localized in ovBNST neurons suggesting that they may be released from the same cells. Together, we showed that NT and Dyn are key modulators of CeA inputs to ovBNST, paving the way to determine whether different conditions or states can alter the neuropeptidergic regulation of this particular brain circuit.

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