Abstract
A growing body of evidence suggests that nucleus accumbens (NAc) plays a significant role not only in the physiological processes associated with reward and satisfaction but also in many diseases of the central nervous system. Summary of the current state of knowledge on the morphological and functional basis of such a diverse function of this structure may be a good starting point for further basic and clinical research. The NAc is a part of the brain reward system (BRS) characterized by multilevel organization, extensive connections, and several neurotransmitter systems. The unique role of NAc in the BRS is a result of: (1) hierarchical connections with the other brain areas, (2) a well-developed morphological and functional plasticity regulating short- and long-term synaptic potentiation and signalling pathways, (3) cooperation among several neurotransmitter systems, and (4) a supportive role of neuroglia involved in both physiological and pathological processes. Understanding the complex function of NAc is possible by combining the results of morphological studies with molecular, genetic, and behavioral data. In this review, we present the current views on the NAc function in physiological conditions, emphasizing the role of its connections, neuroplasticity processes, and neurotransmitter systems.
Highlights
A group of morphologically and functionally related brain structures receiving and interpreting stimuli associated with satisfaction, positive feeling, and addiction is commonly defined as the brain reward system (BRS)
Through the inhibitory effect exerted upon glutamatergic projections in nucleus accumbens (NAc), GABAARs and GABABRs participate in enhancement of the inhibitory effect of ethanol, which leads to disruption in the reward system’s functioning
In the NAc shell of the DA Transporter (DAT) knock-out mice exposed to cocaine, DA level can be raised due to preventing its uptake by the NE transporter [281,282]
Summary
The sources of dopaminergic projections that reach the NAc shell and core are VTA and SN, two mesencephalic structures involved in functioning of the limbic and motor systems, respectively [45,46,47]. One of the most important functions of DA in NAc is its modulatory effect on the processes of short- and long-term homeostatic synaptic plasticity [59,60] It often requires an interaction with other neurotransmitter systems, such as glutamatergic, noradrenergic, and serotonergic [2,56,61]. The modulatory effect of DA is based on regulation of the amount of neurotransmitters released in the area of dendritic spines [62], receptor externalization [59], and trafficking of AMPAR, GluA1, NMDAR receptors [59,63,64] All these processes occurring in the BRS require involvement and cooperation among receptors representing all major neurotransmitter systems [56]. The most important part of this system are dopaminergic neurons located in the VTA which project to the NAc and elaborate behavioral responses initiated by addictive drugs or other forms of rewarding stimuli [67]. The dopaminergic system has a multidirectional effect on the neuronal activity and on the synaptic plasticity and molecular processes related to the gene expression and epigenetic modifications [69,70]
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