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

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.

Download Full-text

Cellular Mechanisms Underlying Antiepileptic Effects of Low- and High-Frequency Electrical Stimulation in Acute Epilepsy in Neocortical Brain Slices In Vitro

Journal of Neurophysiology ◽

10.1152/jn.00514.2006 ◽

2007 ◽

Vol 97 (3) ◽

pp. 1887-1902 ◽

Cited By ~ 77

Author(s):

Yitzhak Schiller ◽

Yael Bankirer

Keyword(s):

Electrical Stimulation ◽

High Frequency ◽

Brain Slices ◽

Low Frequency ◽

High Frequency Stimulation ◽

Dependent Manner ◽

Cellular Mechanisms ◽

Epileptiform Discharges ◽

Frequency Stimulation

Approximately 30% of epilepsy patients suffer from drug-resistant epilepsy. Direct electrical stimulation of the epileptogenic zone is a potential new treatment modality for this devastating disease. In this study, we investigated the effect of two electrical stimulation paradigms, sustained low-frequency stimulation and short trains of high-frequency stimulation, on epileptiform discharges in neocortical brain slices treated with either bicuculline or magnesium-free extracellular solution. Sustained low-frequency stimulation (5–30 min of 0.1- to 5-Hz stimulation) prevented both interictal-like discharges and seizure-like events in an intensity-, frequency-, and distance-dependent manner. Short trains of high-frequency stimulation (1–5 s of 25- to 200-Hz stimulation) prematurely terminated seizure-like events in a frequency-, intensity-, and duration-dependent manner. Roughly one half the seizures terminated within the 100-Hz stimulation train ( P < 0.01 compared with control), whereas the remaining seizures were significantly shortened by 53 ± 21% ( P < 0.01). Regarding the cellular mechanisms underlying the antiepileptic effects of electrical stimulation, both low- and high-frequency stimulation markedly depressed excitatory postsynaptic potentials (EPSPs). The EPSP amplitude decreased by 75 ± 3% after 10-min, 1-Hz stimulation and by 86 ± 6% after 1-s, 100-Hz stimulation. Moreover, partial pharmacological blockade of ionotropic glutamate receptors was sufficient to suppress epileptiform discharges and enhance the antiepileptic effects of stimulation. In conclusion, this study showed that both low- and high-frequency electrical stimulation possessed antiepileptic effects in the neocortex in vitro, established the parameters determining the antiepileptic efficacy of both stimulation paradigms, and suggested that the antiepileptic effects of stimulation were mediated mostly by short-term synaptic depression of excitatory neurotransmission.

Download Full-text

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

Journal of Neurophysiology ◽

10.1152/jn.00629.2001 ◽

2002 ◽

Vol 87 (2) ◽

pp. 1155-1158 ◽

Cited By ~ 31

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.

Download Full-text

The different effects of high-frequency stimulation of the nucleus accumbens shell and core on food consumption are possibly associated with different neural responses in the lateral hypothalamic area

Neuroscience ◽

10.1016/j.neuroscience.2015.06.006 ◽

2015 ◽

Vol 301 ◽

pp. 312-322 ◽

Cited By ~ 5

Author(s):

N. Wei ◽

Y. Wang ◽

X. Wang ◽

Z. He ◽

M. Zhang ◽

...

Keyword(s):

Nucleus Accumbens ◽

Food Consumption ◽

High Frequency ◽

Lateral Hypothalamic Area ◽

High Frequency Stimulation ◽

Neural Responses ◽

Nucleus Accumbens Shell ◽

Hypothalamic Area ◽

Frequency Stimulation ◽

Stimulation Of

Download Full-text

Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00209.2010 ◽

2011 ◽

Vol 300 (2) ◽

pp. H565-H573 ◽

Cited By ~ 20

Author(s):

Masahide Harada ◽

Yukiomi Tsuji ◽

Yuko S. Ishiguro ◽

Hiroki Takanari ◽

Yusuke Okuno ◽

...

Keyword(s):

Action Potential ◽

High Frequency ◽

Rabbit Heart ◽

Left Ventricular ◽

High Frequency Stimulation ◽

Electrophysiological Properties ◽

Rate Dependent ◽

Frequency Stimulation ◽

And Control

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF ( n = 18) and control ( n = 17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs) >1,000 ms but significantly shorter at BCLs <400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17–81%), and conduction velocity was significantly decreased in CHF (by 6–20%). In both groups, high-frequency stimulation (BCLs <150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs <150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.

Download Full-text