Dopamine D4 receptor knockout mice exhibit neurochemical changes consistent with decreased dopamine release.
Dopamine D4 receptor (D4R) knockout mice (D4R-/-) provided for unique neurochemical studies designed to understand D4R contributions to dopamine (DA) regulation. In this study, post-mortem brain tissue content of DA did not differ between D4R+/+ and D4R-/- mice in the striatum (Str) or nucleus accumbens core (NAc). However, there was a significant decrease (82%) in the content of 3,4-dihydoxyphenylacetic acid (DOPAC), a major metabolite of DA, in the NAc of D4R-/- mice. Microdialysis studies performed in a region of brain spanning of the dorsal Str and NAc showed lower baseline levels of DA and a significant reduction in KCl-evoked overflow of DA in the D4R-/- mice. Baseline extracellular levels of DOPAC and homovanillic acid were also significantly lower in the D4R-/- mice. In vivo chronoamperometric recordings of KCl-evoked release of DA also showed decreased release of DA in the Str and NAc of the D4R-/- mice. These studies demonstrate a role of D4Rs in presynaptic DA regulation and support the hypothesis that alterations in D4Rs may lead to diminished DA function.
Thomas
Theresa Currier
TC
Department of Anatomy & Neurobiology, University of Kentucky Chandler Medical Center, Lexington, KY 40536, USA.
Kruzich
Paul J
PJ
Joyce
B Matthew
BM
Gash
C R
CR
Suchland
Katherine
K
Surgener
Stewart P
SP
Rutherford
Erin C
EC
Grandy
David K
DK
Gerhardt
Greg A
GA
Glaser
Paul E A
PE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry / Q000379:methods; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D050638:Receptors, Dopamine D4 / Q000172:deficiency*
D015102:3,4-Dihydroxyphenylacetic Acid; D050638:Receptors, Dopamine D4; D011189:Potassium Chloride; D004298:Dopamine; D006719:Homovanillic Acid