Tonic versus phasic DA release in the nucleus accumbens is differentially regulated by pathways that selectively alter DA neuron spontaneous activity and burst firing

2003 ◽  
Vol 60 (1) ◽  
pp. 106-107 ◽  
Author(s):  
A.A. Grace ◽  
A.R. West ◽  
B. Ash ◽  
H. Moore ◽  
S.B. Floresco
Keyword(s):  
Nucleus Accumbens ◽  
Spontaneous Activity ◽  
Burst Firing ◽  
Da Release

scholarly journals Dopamine Release Neuroenergetics in Mouse Striatal Slices

2020 ◽  
Author(s):  
Msema Msackyi ◽  
Yuanxin Chen ◽  
Wangchen Tsering ◽  
Ninghan Wang ◽  
Jingyu Zhao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nucleus Accumbens ◽  
Oxidative Phosphorylation ◽  
Neurodegenerative Disorder ◽  
Dorsal Striatum ◽  
Striatal Slices ◽  
Axonal Projections ◽  
Specific Vulnerability ◽  
Da Release

AbstractParkinson’s disease (PD) is the second most common neurodegenerative disease. Dopamine (DA) neurons in the substantia nigra par compacta with axonal projections to the dorsal striatum (dSTR) degenerate in PD while in contrast, DA neurons in the ventral tegmental area with axonal projections to the ventral striatum including the nucleus accumbens (NAcc) shell, are largely spared. To understand the pathogenesis of PD, it is important to study the neuroenergetics of DA neurons. This study aims to uncover the relative contribution of glycolysis and oxidative phosphorylation (OxPhos) to evoked DA release in the striatum. We measured evoked DA release in mouse striatal brain slices by fast-scan cyclic voltammetry every 2 minutes. Blocking OxPhos caused a greater reduction in evoked DA release in the dSTR compared to the NAcc shell, and blocking glycolysis caused a greater reduction in evoked DA release in the NAcc shell than in the dSTR. Furthermore, when glycolysis was bypassed in favor of direct OxPhos, evoked DA release in the NAcc shell was decreased by ∼50% over 40 minutes whereas evoked DA release in the dSTR was largely unaffected. These results demonstrated that the dSTR relies primarily on OxPhos for energy production to maintain evoked DA release whereas the NAcc shell relies more on glycolysis. Using two-photon imaging, we consistently found that the oxidation level of the DA terminals was higher in the dSTR than in the NAcc shell. Together, these findings partially explain the specific vulnerability of DA terminals in the dSTR to degeneration in PD.Significant statementThe neuroenergetics of dopaminergic neuron is important to understand Parkinson’s disease (PD), a neurodegenerative disorder associated with mitochondrial dysfunctions. However, the relative contributions of glycolysis and oxidative phosphorylation (OxPhos) to presynaptic energy demands in DA terminals are unclear. We addressed this question by measuring DA release in the dorsal striatum and nucleus accumbens (NAcc) shell of mouse brain using FSCV under reagents blocking different energy systems. We found that the NAcc shell relies on both glycolysis and OxPhos to maintain DA release while the dSTR relies heavily on OxPhos. We demonstrate the different neuroenergetics of DA terminals in these two brain areas, providing new fundamentally important insight into the specific vulnerability of DA terminals in the dSTR to degeneration in PD.

scholarly journals Differential dopamine release by psychosis-generating and non-psychosis-generating addictive substances in the nucleus accumbens and dorsomedial striatum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Klara Danielsson ◽  
Rosita Stomberg ◽  
Louise Adermark ◽  
Mia Ericson ◽  
Bo Söderpalm
Keyword(s):  
Drug Abuse ◽  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Negative Symptoms ◽  
Positive Symptoms ◽  
Differential Effects ◽  
Double Probe ◽  
Dorsomedial Striatum ◽  
Da Release

AbstractSchizophrenia is associated with three main categories of symptoms; positive, negative and cognitive. Of these, only the positive symptoms respond well to treatment with antipsychotics. Due to the lack of effect of antipsychotics on negative symptoms, it has been suggested that while the positive symptoms are related to a hyperdopaminergic state in associative striatum, the negative symptoms may be a result of a reduced dopamine (DA) activity in the nucleus accumbens (nAc). Drug abuse is common in schizophrenia, supposedly alleviating negative symptomatology. Some, but not all, drugs aggravate psychosis, tentatively due to differential effects on DA activity in striatal regions. Here this hypothesis was tested in rats by using a double-probe microdialysis technique to simultaneously assess DA release in the nAc and associative striatum (dorsomedial striatum; DMS) following administration of the psychosis-generating substances amphetamine (0.5 mg/kg), cocaine (15 mg/kg) and Δ9-tetrahydrocannabinol (THC, 3 mg/kg), and the generally non-psychosis-generating substances ethanol (2.5 g/kg), nicotine (0.36 mg/kg) and morphine (5 mg/kg). The data show that amphetamine and cocaine produce identical DA elevations both in the nAc and DMS, whereas nicotine increases DA in nAc only. Ethanol and morphine both increased DMS DA, but weaker and in a qualitatively different way than in nAc, suggesting that the manner in which DA is increased might be important to the triggering of psychosis. THC elevated DA in neither region, indicating that the pro-psychotic effects of THC are not related to DA release. We conclude that psychosis-generating substances affect striatal DA release differently than non-psychosis-generating substances.

scholarly journals Selective D2 and D3 receptor antagonists oppositely modulate cocaine responses in mice via distinct postsynaptic mechanisms in nucleus accumbens

2018 ◽  
Author(s):  
Daniel F. Manvich ◽  
Alyssa K. Petko ◽  
Rachel C. Branco ◽  
Stephanie L. Foster ◽  
Kirsten A. Porter-Stransky ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Drugs Of Abuse ◽  
Ex Vivo ◽  
Medium Spiny Neurons ◽  
D3 Receptor ◽  
Receptor Antagonists ◽  
Fast Scan Cyclic Voltammetry ◽  
Spiny Neurons ◽  
Cocaine Responses ◽  
Da Release

AbstractBackgroundThe D3 receptor (D3R) has emerged as a promising pharmacotherapeutic target for the treatment of several diseases including schizophrenia, Parkinson’s disease, and substance use disorders. However, studies investigating the modulatory impact of D3R antagonism on dopamine neurotransmission or the effects drugs of abuse have produced mixed results, in part because D3R-targeted compounds often also interact with D2 receptors (D2R). The purpose of this study was to compare the consequences of selective D2R or D3R antagonism on the behavioral effects of cocaine in mice, and to identify the neurobiological mechanisms underlying their modulatory effects.MethodsWe characterized the effects of selective D2R or D3R antagonism in mice on 1) basal and cocaine-induced locomotor activity, 2) presynaptic dopamine release and clearance in the nucleus accumbens using ex vivo fast scan cyclic voltammetry, and 3) dopamine-mediated signaling in D1-expressing and D2-expressing medium spiny neurons using ex vivo electrophysiology.ResultsPretreatment with the selective D2R antagonist L-741,626 attenuated, while pretreatment with the selective D3R antagonist PG01037 enhanced, the locomotor-activating effects of acute and repeated cocaine administration. While both antagonists potentiated cocaine-induced increases in presynaptic DA release, D3R blockade uniquely facilitated DA-mediated excitation of D1-expressing medium spiny neurons in the nucleus accumbens.ConclusionsSelective D3R antagonism potentiates the behavioral-stimulant effects of cocaine in mice, an effect that is in direct opposition to that produced by selective D2R antagonism or nonselective D2-like receptor antagonists, likely by facilitating D1-mediated excitation in the nucleus accumbens. These findings provide important insights into the neuropharmacological actions of D3R antagonists on mesolimbic dopamine neurotransmission.

scholarly journals Endocannabinoid Modulation of Nucleus Accumbens Microcircuitry and Terminal Dopamine Release

2021 ◽  
Vol 13 ◽  
Author(s):  
Dan P. Covey ◽  
Alyssa G. Yocky
Keyword(s):  
Nucleus Accumbens ◽  
Activity Patterns ◽  
Cell Types ◽  
Neural Architecture ◽  
Afferent Projections ◽  
Complex Interactions ◽  
Distinct Cell ◽  
Afferent Inputs ◽  
Control Terminal ◽  
Da Release

The nucleus accumbens (NAc) is located in the ventromedial portion of the striatum and is vital to valence-based predictions and motivated action. The neural architecture of the NAc allows for complex interactions between various cell types that filter incoming and outgoing information. Dopamine (DA) input serves a crucial role in modulating NAc function, but the mechanisms that control terminal DA release and its effect on NAc neurons continues to be elucidated. The endocannabinoid (eCB) system has emerged as an important filter of neural circuitry within the NAc that locally shapes terminal DA release through various cell type- and site-specific actions. Here, we will discuss how eCB signaling modulates terminal DA release by shaping the activity patterns of NAc neurons and their afferent inputs. We then discuss recent technological advancements that are capable of dissecting how distinct cell types, their afferent projections, and local neuromodulators influence valence-based actions.

scholarly journals HCN2 in cholinergic interneurons of the nucleus accumbens mediates reward response

2021 ◽  
Author(s):  
Jinah Lee ◽  
Marina Weinberger ◽  
Yuki Kawahara ◽  
Jia Cheng ◽  
Gali Umscweif ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Cyclic Nucleotide ◽  
Behavioral Response ◽  
Cholinergic Neurons ◽  
Cholinergic Receptors ◽  
Nerve Terminals ◽  
Cholinergic Interneurons ◽  
Gated Channel ◽  
Cocaine Infusion ◽  
Da Release

Cholinergic interneurons (ChIs) of the nucleus accumbens (NAc) are important for mediating the behavioral response to rewarding stimuli. A major role for these cells is to regulate dopamine (DA) transmission by activating cholinergic receptors at local DAergic nerve terminals. However, the mechanisms that enable cholinergic neurons to enhance DA release in response to reward remain unknown. Here we report that the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) in NAc ChIs mediates an enhancement in DA signaling in response to rewarding stimuli. The HCN current in NAc ChIs and its modulation by DA, as well as the increase in cholinergic efflux by local cocaine infusion were impaired in mice with deletion of HCN2 in cholinergic cells. Enhancement in the DA efflux and signaling in the NAc in response to rewarding stimuli, as well as cocaine conditioning were also dependent on HCN2 in ChIs. These results provide a mechanistic link between the activity of NAc ChIs and reward encoding.

scholarly journals Differences in Nicotine Encoding Dopamine Release between the Striatum and Shell Portion of the Nucleus Accumbens

2018 ◽  
Vol 28 (3) ◽  
pp. 248-261 ◽  
Author(s):  
Yuan-Hao Chen ◽  
Bon-Jour Lin ◽  
Tsung-Hsun Hsieh ◽  
Tung-Tai Kuo ◽  
Jonathan Miller ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
High Frequency ◽  
Dopamine Release ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
High Frequency Stimulation ◽  
Sprague Dawley ◽  
Frequency Stimulation ◽  
Da Release

The aim of this work was to determine the effect of nicotine desensitization on dopamine (DA) release in the dorsal striatum and shell of the nucleus accumbens (NAc) from brain slices. In vitro fast-scan cyclic voltammetry analysis was used to evaluate dopamine release in the dorsal striatum and the NAc shell of Sprague–Dawley rats after infusion of nicotine, a nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (Mec), and an α4β2 cholinergic receptor antagonist (DHβe). DA release related to nicotine desensitization in the striatum and NAc shell was compared. In both structures, tonic release was suppressed by inhibition of the nicotine receptor (via Mec) and the α4β2 receptor (via DHβe). Paired-pulse ratio (PPR) was facilitated in both structures after nicotine and Mec infusion, and this facilitation was suppressed by increasing the stimulation interval. After variable frequency stimulation (simulating phasic burst), nicotine infusion induced significant augmentation of DA release in the striatum that was not seen in the absence of nicotine. In contrast, nicotine reduced phasic DA release in NAc, although frequency augmentation was seen both with and without nicotine. Evaluation of DA release evoked by various trains (high-frequency stimulation (HFS) 100 Hz) of high-frequency stimulation revealed significant enhancement after a train of three or more pulses in the striatum and NAc. The concentration differences between tonic and phasic release related to nicotine desensitization were more pronounced in the NAc shell. Nicotine desensitization is associated with suppression of tonic release of DA in both the striatum and NAc shell that may occur via the α4β2 subtype of nAChR, whereas phasic frequency-dependent augmentation and HFS-related gating release is more pronounced in the striatum than in the NAc shell. Differences between phasic and tonic release associated with nicotine desensitization may underlie processing of reward signals in the NAc shell, and this may have major implications for addictive behavior.

Sham feeding corn oil increases accumbens dopamine in the rat

2006 ◽  
Vol 291 (5) ◽  
pp. R1236-R1239 ◽  
Author(s):  
Nu-Chu Liang ◽  
Andras Hajnal ◽  
Ralph Norgren
Keyword(s):  
Nucleus Accumbens ◽  
Corn Oil ◽  
Distilled Water ◽  
Reverse Phase Hplc ◽  
Reverse Phase ◽  
Sham Feeding ◽  
Coulometric Detection ◽  
Data Support ◽  
Sensory Modalities ◽  
Da Release

Both real and sham feeding of sucrose increase dopamine (DA) overflow in the nucleus accumbens (NAc). Fat is another constituent of foods that is inherently preferred by humans and rodents. We examined the affect of sham feeding corn oil in rats that were food and water deprived overnight. Rats were implanted with guide cannulas aimed at the NAc, as well as gastric fistulas. On alternate days, they were trained to sham lick 100% corn oil or distilled water (dH2O) for 20 min in the morning. Twenty-minute microdialysis samples were taken before, during, and after sham licking. DA and monoamines were analyzed by reverse-phase HPLC with coulometric detection. The results show that DA release in the NAc was significantly increased during sham licking of corn oil compared with the prior baseline (157.5 ± 18.8%, n = 12). During sham licking of dH2O, DA release in the NAc was not changed (93.0 ± 4.0%, n = 15). This experiment demonstrates that sham feeding of corn oil releases accumbens DA in a manner similar to ingestion of sucrose. Although both stimuli may have an olfactory component, sucrose is a gustatory, and 100% corn oil appears to be a trigeminal stimulus. Thus these data support the hypothesis that different sensory modalities produce reward using the same or closely related substrates in the forebrain.

Modulation of Somatodendritic Dopamine Release by Endogenous H2O2: Susceptibility in Substantia Nigra But Resistance in VTA

2002 ◽  
Vol 87 (2) ◽  
pp. 1155-1158 ◽  
Author(s):  
Billy T. Chen ◽  
Marat V. Avshalumov ◽  
Margaret E. Rice
Keyword(s):  
Nucleus Accumbens ◽  
Substantia Nigra ◽  
Dopamine Release ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
Substantia Nigra Pars Compacta ◽  
Fast Scan Cyclic Voltammetry ◽  
Carbon Fiber Microelectrodes ◽  
Da Release ◽  
Striking Contrast

We showed previously that dopamine (DA) release in dorsal striatum is inhibited by endogenously generated hydrogen peroxide (H2O2). Here, we examined whether endogenous H2O2 can also modulate somatodendritic DA release in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), with companion measurements in DA terminal regions. Evoked DA release was monitored in brain slices using carbon-fiber microelectrodes with fast-scan cyclic voltammetry. Exogenous H2O2decreased DA release by 50–60% in SNc and VTA but only by 35% in nucleus accumbens. Whether endogenous H2O2 also modulated somatodendritic release was examined using the glutathione peroxidase inhibitor, mercaptosuccinate (MCS), which should increase stimulation-evoked H2O2levels. In the presence of MCS, DA release was suppressed by 30–40% in SNc as well as in dorsal striatum and nucleus accumbens. In striking contrast, DA release in the VTA was unaffected by MCS. These data are consistent with stronger H2O2 regulation or lower H2O2 generation in VTA than in the other regions. Importantly, oxidative stress has been linked causally to Parkinson's disease, in which DA cells in SNc degenerate, but VTA cells are spared. The present data suggest that differences in oxidant regulation or generation between SNc and VTA could contribute to this.

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