The role of dopamine in the movement and the reward pathway

Dopamine is a neurotransmitter produced mainly in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNPC) in the brain, exhibiting both excitatory and inhibitory effects in different brain pathways. Dopamine is important in mediating the mesolimbic and nigrostriatal pathways for reward and movement, respectively. Therefore, damage to dopaminergic neurones affects dopamine levels in the brain and can consequently result in diseases associated with abnormal dopamine levels.

Movement

The role of dopamine is vital in modulating the initiation of movement through both the direct and indirect pathways of the basal ganglia (figure 1). In the direct pathway, dopamine produced from the SNPC binds to the D1 Gs-coupled receptors in the striatum resulting in the activation of the intracellular signalling cascade. Activation of these receptors results in increased intracellular cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) levels, which control the modulation of ion channels, including calcium channels for further depolarisation of the striatal cells. The excitation of the striatum results in GABAergic inhibition of the globus pallidus internal segment (GPI) and the substantia nigra pars reticulata (SNPR). Hence, this results in the disinhibition of the thalamus, allowing for excitatory glutamatergic transmission to the motor cortex for the facilitation of movement. The activation of the striatum via D1 receptor stimulation can be supported by a study conducted by Gerfen et al. 2012 in which they concluded that PKA activates calcium voltage-gated 1 L-type calcium channels, resulting in depolarisation of striatal cells, which causes the enablement of movement via the direct pathway. However, in the indirect pathway, dopamine binds to D2 Gi-coupled receptors with a higher affinity than D1 receptors, causing inhibition of these receptors and their intracellular signalling cascades. Consequently, there is decreased inhibition of potassium channels by the second messengers, resulting in hyperpolarisation due to potassium efflux from the striatal cells. As the striatum is inactivated, this reduces the overall inhibitory effect of the indirect pathway on the thalamus, allowing for movement. Therefore, dopamine is critical for the normal functioning of humans by allowing them to control their movements for survival, for example, by pushing a ball away when it is about to hit them.

Reward Pathway

The mesolimbic dopaminergic pathway (figure 2) is the most recognised reward pathway in the brain. This pathway contains the VTA, located in the midbrain, the nucleus accumbens (NA) and the tuberculum olfactorium (TO), located in the basal forebrain. The lateral regions of the VTA are the most abundant in A10 dopaminergic neurones in comparison to other regions of the VTA. These A10 neurones are activated in association with reward anticipation, for example, after exercising. The medial VTA dopaminergic neurones project to the core and medial shell regions of the NA, and the lateral VTA project towards the lateral shell region of the NA (figure 3). Thus, increasing dopamine levels in the NA and inducing the processing of the reward. Moreover, dopaminergic inputs from the VTA to the TO allow the individual to develop an odour preference for a specific stimulus due to motivation-oriented behaviour. Hence, this could be a reason why the anticipation of eating one's favourite food by evoking the memory of its smell is associated with the feeling of reward. Experiments conducted by FitzGerald et al. 2014 support my points regarding the role of the TO in the mesolimbic pathway. In their study, mice were given a choice of two different odours to choose from. The team noted activation of c-Fos neurones in the forebrain, indicating neuronal activity in this region, which is involved in reward motivation behaviour. Hence, allowing them to support the importance of the TO in odour processing and reward behaviour in the mice when choosing a more pleasurable odour. Eventually, projections from the TO and NA converge at the ventral pallidum, where the enrichment of reward-related learning occurs. Therefore, dopamine is essential for the initiation of the reward pathway in ensuring the continuation of reward behaviour when exposed to a specific stimulus and for survival due to the association of reproduction with reward.

Conclusion

In conclusion, dopamine is essential for the initiation of movement and in the reward pathway for normal human functioning and survival. Studies into aldehyde-dehydrogenase 1 in the SNPC have found that it protects dopaminergic neurones against neurodegeneration. Further studies will aid in understanding the mechanisms by which this enzyme is regulated and the actions by which it protects dopaminergic neurones in the SNPC.

Written by Maria Z Kahloon

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