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High-frequency electrical stimulation in the nucleus accumbens of morphine-treated rats suppresses neuronal firing in reward-related brain regions.

Hu WH, Bi YF, Zhang K, Meng FG, Zhang JG - Med. Sci. Monit. (2011)

Bottom Line: Conditioned place preference (CPP) behavior of the rats was evaluated to confirm morphine preference after morphine injection and CPP training for 10 days.The results suggest that electrical stimulation in the NAc can suppress neuronal firing in reward-related brain regions.The core and shell of the NAc play different roles in suppressing NAc neuronal firing as 2 stimulating targets.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

ABSTRACT

Background: Previous studies have reported that high-frequency stimulation (HFS) in the nucleus accumbens (NAc) is a potential treatment modality for drug craving and relapse. We aimed to explore the electrophysiological changes in reward-related brain regions during NAc stimulation and reveal the effects of stimulation frequency and target changes on NAc neuronal activities.

Material/methods: Twenty-eight rats were randomized into saline (n=8) and morphine (n=20) groups. The morphine group was further divided into core (n=10, only the core of the NAc was stimulated) and shell (n=10, only the shell of the NAc was stimulated) subgroups. Conditioned place preference (CPP) behavior of the rats was evaluated to confirm morphine preference after morphine injection and CPP training for 10 days. We recorded NAc neuronal responses to NAc core stimulation at different frequencies, as well as changes in VP and VTA neuronal firing during NAc core stimulation, and changes in NAc neuronal firing during NAc shell stimulation.

Results: The results indicate that high frequency stimulation was more effective in suppressing NAc neuronal activities than low frequency stimulation and that core stimulation was more effective than shell stimulation. Most VP neurons were inhibited by NAc core stimulation, while VTA neurons were not.

Conclusions: The results suggest that electrical stimulation in the NAc can suppress neuronal firing in reward-related brain regions. The stimulation might be frequency- dependent in suppressing neuronal firing. The core and shell of the NAc play different roles in suppressing NAc neuronal firing as 2 stimulating targets.

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Electrical stimulation of the NAc core suppressed firing of NAc neurons. (A) Distribution of responses of NAc neurons (n=27) to NAc core stimulation. The number of inhibited neurons increased from 11 (40.7%) to 22 (81.5%) as the stimulation frequency increased from 20 Hz to 200 Hz. (B). Firing rates of NAc neurons (n=27) before, during and after NAc core stimulation at different frequencies. Firing rates were suppressed during stimulation and recovered to pre-stimulation levels after stimulation. Data was mean ±SEM, * stood for P<0.05 as compared with the pre-stimulation levels, Paired-Samples t test, # stood for P<0.05 as compared with the post-stimulation levels, Paired-Samples t test. (C). Suppression rates of NAc neuronal (n=27) firing during NAc core stimulation at different frequencies. Data was mean ±SEM, * stood for P<0.05 as compared with the suppression rate at 130Hz, ANOVA, Fisher’s LSD. (D). During NAc core stimulation, neurons inhibited were closer to stimulation sites than those with no response at 130Hz (0.90±0.06 mm vs. 1.20±0.11 mm). Data was mean ±SEM, * stood for P<0.05, Independent-Sample t test.
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f4-medscimonit-17-6-br153: Electrical stimulation of the NAc core suppressed firing of NAc neurons. (A) Distribution of responses of NAc neurons (n=27) to NAc core stimulation. The number of inhibited neurons increased from 11 (40.7%) to 22 (81.5%) as the stimulation frequency increased from 20 Hz to 200 Hz. (B). Firing rates of NAc neurons (n=27) before, during and after NAc core stimulation at different frequencies. Firing rates were suppressed during stimulation and recovered to pre-stimulation levels after stimulation. Data was mean ±SEM, * stood for P<0.05 as compared with the pre-stimulation levels, Paired-Samples t test, # stood for P<0.05 as compared with the post-stimulation levels, Paired-Samples t test. (C). Suppression rates of NAc neuronal (n=27) firing during NAc core stimulation at different frequencies. Data was mean ±SEM, * stood for P<0.05 as compared with the suppression rate at 130Hz, ANOVA, Fisher’s LSD. (D). During NAc core stimulation, neurons inhibited were closer to stimulation sites than those with no response at 130Hz (0.90±0.06 mm vs. 1.20±0.11 mm). Data was mean ±SEM, * stood for P<0.05, Independent-Sample t test.

Mentions: Although only 40.7% of neurons were inhibited by core stimulation at 20 Hz (Figure 4A), the general effect was inhibitory (Paired-Samples t test: t(26)=3.44, P=0.002) (Figure 4B). The firing rates of most neurons tested in the NAc (66.7%~81.5%) showed a significant decrease in response to core stimulation at frequencies from 50 Hz to 200 Hz (Paired-Samples t test: 50 Hz, t(26)=5.32, P<0.0001; 80 Hz, t(26)=5.27, P<0.0001; 130 Hz, t(26)=5.79, P<0.0001; 200 Hz, t(26)=6.31, P<0.0001). The suppression rate increased (from 25.80±7.04% to 65.95±6.83%) as the frequency increased. Compared with stimulation at 130 Hz, only stimulation at 20 Hz showed a significantly lower suppression rate (ANOVA, Fisher’s LSD: P=0.20 <0.05) (Figure 4C). The neuronal firing rate recovered to baseline levels immediately after the electrical stimulation discontinued (Figure 4B).


High-frequency electrical stimulation in the nucleus accumbens of morphine-treated rats suppresses neuronal firing in reward-related brain regions.

Hu WH, Bi YF, Zhang K, Meng FG, Zhang JG - Med. Sci. Monit. (2011)

Electrical stimulation of the NAc core suppressed firing of NAc neurons. (A) Distribution of responses of NAc neurons (n=27) to NAc core stimulation. The number of inhibited neurons increased from 11 (40.7%) to 22 (81.5%) as the stimulation frequency increased from 20 Hz to 200 Hz. (B). Firing rates of NAc neurons (n=27) before, during and after NAc core stimulation at different frequencies. Firing rates were suppressed during stimulation and recovered to pre-stimulation levels after stimulation. Data was mean ±SEM, * stood for P<0.05 as compared with the pre-stimulation levels, Paired-Samples t test, # stood for P<0.05 as compared with the post-stimulation levels, Paired-Samples t test. (C). Suppression rates of NAc neuronal (n=27) firing during NAc core stimulation at different frequencies. Data was mean ±SEM, * stood for P<0.05 as compared with the suppression rate at 130Hz, ANOVA, Fisher’s LSD. (D). During NAc core stimulation, neurons inhibited were closer to stimulation sites than those with no response at 130Hz (0.90±0.06 mm vs. 1.20±0.11 mm). Data was mean ±SEM, * stood for P<0.05, Independent-Sample t test.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3539543&req=5

f4-medscimonit-17-6-br153: Electrical stimulation of the NAc core suppressed firing of NAc neurons. (A) Distribution of responses of NAc neurons (n=27) to NAc core stimulation. The number of inhibited neurons increased from 11 (40.7%) to 22 (81.5%) as the stimulation frequency increased from 20 Hz to 200 Hz. (B). Firing rates of NAc neurons (n=27) before, during and after NAc core stimulation at different frequencies. Firing rates were suppressed during stimulation and recovered to pre-stimulation levels after stimulation. Data was mean ±SEM, * stood for P<0.05 as compared with the pre-stimulation levels, Paired-Samples t test, # stood for P<0.05 as compared with the post-stimulation levels, Paired-Samples t test. (C). Suppression rates of NAc neuronal (n=27) firing during NAc core stimulation at different frequencies. Data was mean ±SEM, * stood for P<0.05 as compared with the suppression rate at 130Hz, ANOVA, Fisher’s LSD. (D). During NAc core stimulation, neurons inhibited were closer to stimulation sites than those with no response at 130Hz (0.90±0.06 mm vs. 1.20±0.11 mm). Data was mean ±SEM, * stood for P<0.05, Independent-Sample t test.
Mentions: Although only 40.7% of neurons were inhibited by core stimulation at 20 Hz (Figure 4A), the general effect was inhibitory (Paired-Samples t test: t(26)=3.44, P=0.002) (Figure 4B). The firing rates of most neurons tested in the NAc (66.7%~81.5%) showed a significant decrease in response to core stimulation at frequencies from 50 Hz to 200 Hz (Paired-Samples t test: 50 Hz, t(26)=5.32, P<0.0001; 80 Hz, t(26)=5.27, P<0.0001; 130 Hz, t(26)=5.79, P<0.0001; 200 Hz, t(26)=6.31, P<0.0001). The suppression rate increased (from 25.80±7.04% to 65.95±6.83%) as the frequency increased. Compared with stimulation at 130 Hz, only stimulation at 20 Hz showed a significantly lower suppression rate (ANOVA, Fisher’s LSD: P=0.20 <0.05) (Figure 4C). The neuronal firing rate recovered to baseline levels immediately after the electrical stimulation discontinued (Figure 4B).

Bottom Line: Conditioned place preference (CPP) behavior of the rats was evaluated to confirm morphine preference after morphine injection and CPP training for 10 days.The results suggest that electrical stimulation in the NAc can suppress neuronal firing in reward-related brain regions.The core and shell of the NAc play different roles in suppressing NAc neuronal firing as 2 stimulating targets.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

ABSTRACT

Background: Previous studies have reported that high-frequency stimulation (HFS) in the nucleus accumbens (NAc) is a potential treatment modality for drug craving and relapse. We aimed to explore the electrophysiological changes in reward-related brain regions during NAc stimulation and reveal the effects of stimulation frequency and target changes on NAc neuronal activities.

Material/methods: Twenty-eight rats were randomized into saline (n=8) and morphine (n=20) groups. The morphine group was further divided into core (n=10, only the core of the NAc was stimulated) and shell (n=10, only the shell of the NAc was stimulated) subgroups. Conditioned place preference (CPP) behavior of the rats was evaluated to confirm morphine preference after morphine injection and CPP training for 10 days. We recorded NAc neuronal responses to NAc core stimulation at different frequencies, as well as changes in VP and VTA neuronal firing during NAc core stimulation, and changes in NAc neuronal firing during NAc shell stimulation.

Results: The results indicate that high frequency stimulation was more effective in suppressing NAc neuronal activities than low frequency stimulation and that core stimulation was more effective than shell stimulation. Most VP neurons were inhibited by NAc core stimulation, while VTA neurons were not.

Conclusions: The results suggest that electrical stimulation in the NAc can suppress neuronal firing in reward-related brain regions. The stimulation might be frequency- dependent in suppressing neuronal firing. The core and shell of the NAc play different roles in suppressing NAc neuronal firing as 2 stimulating targets.

Show MeSH
Related in: MedlinePlus