Controlled cortical impact injury affects dopaminergic transmission in the rat striatum.
The therapeutic benefits of dopamine (DA) agonists after traumatic brain injury (TBI) imply a role for DA systems in mediating functional deficits post-TBI. We investigated how experimental TBI affects striatal dopamine systems using fast scan cyclic voltammetry (FSCV), western blot, and d-amphetamine-induced rotational behavior. Adult male Sprague-Dawley rats were injured by a controlled cortical impact (CCI) delivered unilaterally to the parietal cortex, or were naïve controls. Amphetamine-induced rotational behavior was assessed 10 days post-CCI. Fourteen days post-CCI, animals were anesthetized and underwent FSCV with bilateral striatal carbon fiber microelectrode placement and stimulating electrode placement in the medial forebrain bundle (MFB). Evoked DA overflow was assessed in the striatum as the MFB was electrically stimulated at 60 Hz for 10 s. In 23% of injured animals, but no naïve animals, rotation was observed with amphetamine administration. Compared with naïves, striatal evoked DA overflow was lower for injured animals in the striatum ipsilateral to injury (p < 0.05). Injured animals exhibited a decrease in V(max) (52% of naïve, p < 0.05) for DA clearance in the hemisphere ipsilateral to injury compared with naïves. Dopamine transporter (DAT) expression was proportionally decreased in the striatum ipsilateral to injury compared with naïve animals (60% of naïve, p < 0.05), despite no injury-related changes in vesicular monoamine transporter or D2 receptor expression (DRD2) in this region. Collectively, these data appear to confirm that the clinical efficacy of dopamine agonists in the treatment of TBI may be related to disruptions in the activity of subcortical dopamine systems.
Wagner
A K
AK
Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pennsylvania 15213, USA. wagnerak@upmc.edu
Sokoloski
J E
JE
Ren
D
D
Chen
X
X
Khan
A S
AS
Zafonte
R D
RD
Michael
A C
AC
Dixon
C E
CE
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D001930:Brain Injuries / Q000503:physiopathology* / Q000523:psychology; D002540:Cerebral Cortex / Q000293:injuries*; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004594:Electrophysiology; D007700:Kinetics; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D017072:Neostriatum / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012399:Rotation; D009435:Synaptic Transmission / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D014446:Tyrosine 3-Monooxygenase; D003913:Dextroamphetamine; D004298:Dopamine