Direct, real-time assessment of dopamine release autoinhibition in the rat caudate-putamen.
Inhibition of endogenous dopamine release by photo-released dopamine (i.e., autoinhibition) was characterized in the rat caudate-putamen using combined caged-dopamine photolysis and fast-scan cyclic voltammetry. Coronal brain slices (400 microm thick) were perfused with caged-dopamine (150-200 microM in artificial cerebrospinal fluid). Ultraviolet illumination of increasing duration (25-250 ms, approximately 100 microm beam diameter) was focused at the tip of the recording electrode to uncage increasing amounts of exogenous dopamine at the recording sites (0.5-5 microM); a single biphasic electrical stimulus was delivered 0.1-10 s later to induce endogenous dopamine release. The concentrations of both endogenous and exogenous dopamine were determined using voltammetry, thus enabling determination of concentration-dependent inhibition of the endogenous release by the latter. While unaffected by control ultraviolet illumination, endogenous dopamine release was rapidly inhibited by photo-released dopamine in a concentration-dependent manner. Photo-application of 3-5 microM exogenous dopamine inhibited the endogenous release by 90-100% (electrical stimulus applied 1 s after photolysis initiation), an effect prevented by 2 microM sulpiride. The autoinhibition was dependent on the time between photolysis onset and electrical stimulation. Terminal dopamine autoreceptor stimulation led to robust inhibition of endogenous dopamine release with a latency of approximately 200 ms and effective duration of less than 5 s. The percent autoinhibition was a skewed, U-shaped function of photolysis/electrical stimulation intervals with the peak inhibition at 1 s. This study directly demonstrates that autoreceptor-mediated inhibition of terminal dopamine release in caudate-putamen is designed to provide a rapid, robust, yet short-lasting modulation of terminal dopamine release.
Lee
T H
TH
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. leedopam@duke.edu
Gee
K R
KR
Davidson
C
C
Ellinwood
E H
EH
D000818:Animals; D002421:Caudate Nucleus / Q000378:metabolism* / Q000528:radiation effects; D003199:Computer Systems; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009994:Osmolar Concentration; D010782:Photolysis; D011699:Putamen / Q000378:metabolism* / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004298:Dopamine