Pritam Dutta, M.Optom, FAAO

ERC Eye Hospital, Sibsagar, Assam, India


Alternation in the dopamine transporter expression following TBI

Dopamine transporters (DATs), membrane proteins that transfer dopamine from the synapse to the cytosol, play a role in dopamine neurotransmission. (1) DAT levels fell constantly after TBI, according to multiple studies, and the pace at which DAT takes dopamine from the synapse could have a significant impact on dopamine levels in the cell.(2, 3) DAT deficient mice have severe cognitive impairments, hyperactivity, and motor abnormalities, demonstrating this. As a result, decreased DAT expression following TBI could lead to decreased dopamine neurotransmission in the brain. Because dopamine neurons in the retrorubral field (RRF) project to the amygdala, striatum, bed nucleus of the stria terminalis, and hippocampal formation, decreased DAT expression in the RRF could create problems in these areas as well.(2,3)

Effects of dopamine-related genes on neurobehavioral recovery after a traumatic brain injury

Dopamine may play a role in plasticity by promoting synaptogenesis and neuronal sprouting, as well as motor function recovery after TBI, cognitive reserve, and the therapy of cognitive deficiencies after TBI.(4,5) As a result, mutations in genes implicated in the dopaminergic system may have a significant impact on behavioural outcomes following TBI. Candidate genes include those coding for dopamine receptor subtypes, dopamine reuptake (DAT), and dopamine metabolism (catechol-o-methyl transferase or COMT).(6) Interestingly, positron emission tomography (PET) studies have shown changes in striatal D2 binding following working memory training (7), and lower dopamine D2 receptor densities have been associated with better motor sequence learning in healthy adults. According to investigations, the ANKK1 and SLC6A3 genes may provide increased cognitive (8) or neural (9) plasticity, which may be particularly important for brain damage recovery.

Dopaminergic Drug Mechanisms of Action and Beneficial Effects on Brain Injury

Drugs that modulate dopaminergic transmission have been shown in previous studies to improve cognitive recovery, executive function, attentional function, processing speed, and memory in TBI patients during rehabilitation.(10-12) Blockade of the dopamine transporter, inhibition of dopamine reuptake, and facilitation of dopamine production are some of the mechanisms of action of dopaminergic medications used to treat TBI patients. The Neurotrauma Foundation recommends methylphenidate, amantadine, and bromocriptine as among the most effective medications.(10)

Does alteration in dopamine levels following TBI impact visual function?

Following a concussion, lesioning the midbrain dopamine cells reduces the attentive component of behaviour, either by reducing the frequency of saccades or by disregarding intriguing stimuli. The basal ganglia (BG), which is known to govern the preparation of saccades in the superior colliculus by persistent inhibition, is one important site of dopaminergic innervation.(13)


The dopamine system is a unique TBI approach that optimizes functional outcomes. TBI has the potential to harm the dopaminergic system. Dopamine levels can affect cellular dysfunction and inflammation in the central nervous system (CNS). Dopamine should be regarded a first-line treatment to protect cerebral autoregulation and improve brain outcomes in TBI, according to experimental findings. In addition, looking into dopamine-related genetic characteristics in relation to injury severity could be very useful in advancing TBI treatment. Importantly, numerous clinical lines of evidence have shown that many dopamine agonists are useful when given to TBI patients after an injury. However, dopamine treatment has side effects that prevent it from being used in TBI treatment, so ongoing large, prospective, double-blind randomized controlled trials (RCTs) with these medications using standardized criteria and outcomes are needed to fully understand their effectiveness in this patient group.



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  2. Haleem DJ. Extending therapeutic use of psychostimulants: focus on serotonin-1A receptor. Prog Neuropsychopharmacol Biol Psychiatry. 2013;46:170–80.
  3. Hu Z, Cooper M, Crockett DP, Zhou R. Differentiation of the midbrain dopaminergic pathways during mouse development. J Comp Neurol. 2004;476:301–11
  4. Stroemer RP, Kent TA, Hulsebosch CE. Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats. 1998;29:2381–2393.
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  9. Klingberg T. Childhood cognitive development as a skill. Trends Cogn Sci. 2014;18:573–579.
  10. Bales, J. W., Yan, H. Q., Ma, X., Li, Y., Samarasinghe, R., and Dixon, C. E. (2011). The dopamine and cAMP regulated phosphoprotein, 32 kDa (DARPP-32) signaling pathway: A novel therapeutic target in traumatic brain injury.  Neurol.229, 300–307. doi: 10.1016/j.expneurol.2011.02.013
  11. Frenette, A. J., Kanji, S., Rees, L., Williamson, D. R., Perreault, M. M., Turgeon, A. F., et al. (2011). Efficacy and Safety of Dopamine Agonists in Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials.  Neurotrauma.29, 1–18. doi: 10.1089/neu.2011.1812
  12. Plummer, N. R., Tam, A. W. F., Mulvaney, C. A., Preston, N. J., and Laha, S. K. (2018). Dopamine agonists for traumatic brain injury. Cochrane Database Syst. Rev.2018:CD013062.
  13. Hikosaka, O., Takikawa, Y., Kawagoe, R.: Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol. Rev. 80(3), 953–978 (2000)


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