Elsevier

Neuroscience

Volume 169, Issue 1, 11 August 2010, Pages 132-142
Neuroscience

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
In vivo voltammetric monitoring of catecholamine release in subterritories of the nucleus accumbens shell

https://doi.org/10.1016/j.neuroscience.2010.04.076Get rights and content

Abstract

Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes has been used to demonstrate that sub-second changes in catecholamine concentration occur within the nucleus accumbens (NAc) shell during motivated behaviors, and these fluctuations have been attributed to rapid dopamine signaling. However, FSCV cannot distinguish between dopamine and norepinephrine, and caudal regions of the NAc shell receive noradrenergic projections. Therefore, in the present study, we examined the degree to which norepinephrine contributes to catecholamine release within rostral and caudal portion of NAc shell. Analysis of tissue content revealed that dopamine was the major catecholamine detectable in the rostral NAc shell, whereas both dopamine and norepinephrine were found in the caudal subregion. To examine releasable catecholamines, electrical stimulation was used to evoke release in anesthetized rats with either stimulation of the medial forebrain bundle, a pathway containing both dopaminergic and noradrenergic projections to the NAc, or the ventral tegmental area/substantia nigra, the origin of dopaminergic projections. The catecholamines were distinguished by their responses to different pharmacological agents. The dopamine autoreceptor blocker, raclopride, as well as the monoamine and dopamine transporter blockers, cocaine and GBR 12909, increased evoked catecholamine overflow in both the rostral and caudal NAc shell. The norepinephrine autoreceptor blocker, yohimbine, and the norepinephrine transporter blocker, desipramine, increased catecholamine overflow in the caudal NAc shell without significant alteration of evoked responses in the rostral NAc shell. Thus, the neurochemical and pharmacological results show that norepinephrine signaling is restricted to caudal portions of the NAc shell. Following raclopride and cocaine or raclopride and GBR 12909, robust catecholamine transients were observed within the rostral shell but these were far less apparent in the caudal NAc shell, and they did not occur following yohimbine and desipramine. Taken together, the data demonstrate that catecholamine signals in the rostral NAc shell detected by FSCV are due to change in dopamine transmission.

Section snippets

Animals

Adult male Sprague–Dawley rats (320–400 g) were purchased from Charles Rivers (Wilmington, MA, USA) and housed in temperature and humidity controlled rooms with ad libitum food and water with a 12/12 h light/dark cycle. All procedures for handling and caring for the laboratory animals were in accordance with the NIH Guide for Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee of the University of North Carolina at Chapel Hill.

Surgery

Rats were

Catecholamine content of the rostral and caudal NAc shell

The rostral and caudal NAc shell were dissected from fresh brains and their catecholamine content determined by HPLC (Table 1). The dopamine tissue content in the rostral and caudal NAc regions was not significantly different (t=0.99, df =25, P=0.33). Dopamine was a major catecholamine in the rostral NAc shell. Only a very low amount of norepinephrine was found (norepinephrine was present in 1 of 15 samples from five rats), but both dopamine and norepinephrine were present in significant

Discussion

Here, we examined the evoked release of catecholamines in two NAc sub regions with FSCV. The sensor employed, the carbon-fiber microelectrode, has micron dimensions allowing investigation of these two sub regions that are only separated by ∼800 μm. Catecholamine release was evoked by either stimulation of the MFB, a major ascending pathway that contains both dopaminergic and noradrenergic neurons (Ungerstedt, 1971), or the VTA/SN region. Stimulation in the latter region activates dopamine cell

Conclusion

The present results show that norepinephrine is regulated in the caudal NAc shell by norepinephrine autoreceptors and uptake transporters. This result suggests that dopaminergic and noradrenergic transmission within the caudal NAc shell may play significantly different roles in regulating the behavioral and physiologic responses associated with drug abuse, physical stressors and other rewarding and aversive stimuli, compared to the rostral NAc shell.

Acknowledgments

We thank Khristy Fontillas for providing technical assistance and thank Richard B. Keithley and Dr. Nii Addy for supporting data analysis. This work was supported by NIH (NS 15841 to RMW and DA 17318 to RMC and RMW).

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