Differential effect of a dopaminergic agonist on prefrontal function in traumatic brain injury patients

Abstract

We examined the effects of low-dose bromocriptine, a D2 dopamine receptor agonist, on processes thought to be subserved by the prefrontal cortex, including working memory and executive function, in individuals with traumatic brain injury. A group of 24 subjects was tested using a double-blind, placebo-controlled crossover trial, counterbalanced for order. Bromocriptine was found to improve performance on some tasks thought to be subserved by prefrontal function, but not others. Specifically, there was improvement in performance on clinical measures of executive function and in dual-task performance, but not measures that tap the ability to maintain information in working memory without significant executive demands. Also, on control tasks not thought to be dependent on the prefrontal cortex, no improvement on bromocriptine was noted. These results demonstrate a selective effect of bromocriptine on cognitive processes which involve executive control, and provide a foundation for potential therapies for patients with prefrontal damage causing dysexecutive syndromes.

Acute treatment with the 5-HT1A receptor agonist 8-OH-DPAT and chronic environmental enrichment confer neurobehavioral benefit after experimental brain trauma

“…5-HT 1A receptor agonists also increase dopamine (DA) levels [3,85], which may confer benefit by restoring DA neurotransmission in a system that is known to be altered after TBI [22,43,49,61,65,98,102,103]. Evidence to support this assertion comes from studies showing that the DA receptor agonists amantadine, bromocriptine, and methylphenidate improve functional outcome and/or preserve hippocampal CA 3 cell survival after TBI [20,47,[51][52][53]64,77,99]. A potential mechanism for the EE-induced benefits may include neural-adaptive changes such as increased hippocampal neurogenesis [10,45,71].…”

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT1A-Receptor Agonist Buspirone

“…One strategy that has received considerable attention is the administration of pharmacological agents, acting either as agonists or antagonists, on various neurotransmitter systems. Of these, the catecholaminergic, cholinergic, and glutamatergic neurotransmitter systems have received overwhelming consideration as potential targets for therapeutic intervention (Bales et al, 2009;Dixon et al, 1997Dixon et al, ,1999Kline et al, 2002aKline et al, ,2004bKokiko and Hamm, 2007;McDowell et al, 1998;Parton et al, 2005;Sutton and Feeney, 1992;Temple and Hamm, 1996;Verbois et al, 2003; also see reviews by Garcia et al, 2011 andWheaton et al, 2009). In contrast, the serotonergic (5-hydroxytryptamine; 5-HT) system has received sparse attention after TBI, with just a few reports describing the behavioral consequences of altering 5-HT neurotransmission (Bañ os et al, 2010;Wang et al, 2011;Wilson and Hamm, 2002).…”

Differences in cognitive impairment of relapsing remitting, secondary, and primary progressive MS

“…9,23 It might be hypothesized that blood-brain barrier disruption interferes with normal transport ratios of neurotransmitter precursors across the blood-brain barrier, leading to specific neurotransmitter imbalances, or that the blood-brain barrier becomes more permeable, resulting in an increase of toxins in the brain. Such mechanisms may be associated specifically with poor performance on the WLG and the 10/36 SRT, considering the fact that the WM operations required by these tasks were shown to be very sensitive to catecholaminergic modulation [24][25][26] and proinflammatory cytokines. 27,28 Future studies aiming at elucidating the pathophysiology of cognition in different forms of MS should employ sensitive cognitive tests that strongly demand (central or peripheral) processing speed and few other cognitive operations and tasks that require high-order WM operations without an explicit demand for information-processing speed.…”