The role of dopamine neurotransmission in concussion-induced working memory deficits

Robert Anthony Laskowski

doi:10.17918/00008795

Concussion is a traumatically-induced short-lived neurological dysfunction lacking visible structural abnormalities via standard neuroimaging, with an estimated annual incidence of 1.6-3.8 million cases. Approximately 20-30% of mild traumatic brain injuries in the 8-19 year-old age group are concussions, resulting primarily from contact sports. A major consequence of concussion is impairment of working memory, which typically resolves in 7-10 days. I developed a model of concussion in the juvenile rat which is neurologically equivalent to the adolescent human. Impact over the frontal cortex of 5-week-old male rats resulted in working memory deficits over the first 3 days post-injury which was associated with blunted evoked field potentials and decreased synaptic transmission within the anterior cingulate cortex at 1 day post-injury. Although overt degenerative changes were not observed, blood-brain barrier permeability along with reactive astrocytosis was apparent underneath the site of impact. The neurotransmitter dopamine plays an important role in regulating working memory and has been implicated in post-traumatic cognitive dysfunction in adult animals. Concussion in the juvenile rat resulted in a four-fold increase in extracellular dopamine within 5 minutes which led an internalization of the D1 receptor at 6 hours post-injury; administration of the D1 antagonist SCH23390 blocked injury-induced receptor internalization but did not affect working memory impairment. In contrast, treatment of brain-injured rats with the partial D1 receptor agonist SKF38393 resulted in an improved working memory function. At 3-7 days post-injury, there was a decrease in tyrosine hydroxylase expression which was accompanied by an increase in the surface expression of the D1 receptor. Interestingly, the evoked field potentials in slices from brain-injured rats were not restored with exogenous dopamine and were less sensitive to SCH23390 suggesting a possible D1 receptor dysfunction. Similarly, evoked field potentials at 1 day post-injury appeared to be less sensitive to the D2 receptor antagonist sulpiride; preliminary observations suggest that sulpiride may exacerbate post-traumatic working memory deficits. In contrast, the D2 agonist bromocriptine did not affect post-concussion working memory impairment. Collectively, my data suggest that dopamine may play an important role in concussion-induced cognitive disturbances and may provide strategies for improving function in the acute post-traumatic period.

The role of dopamine neurotransmission in concussion-induced working memory deficits

Files and links (1)

Abstract

Metrics

Details

The role of dopamine neurotransmission in concussion-induced working memory deficits

Files and links (1)

Abstract

Metrics

Details

Drexel University Social media