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Individual Differences to Cocaine‐Induced Activation in Rats: Striatal Dopamine D1 and D2 Receptors
Author(s) -
Rorabaugh Jacki Marie,
Larson Gaynor A,
Zahniser Nancy R
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.766.3
Subject(s) - dopamine receptor d2 , striatum , dopamine transporter , raclopride , dopamine uptake inhibitors , nucleus accumbens , dopamine , sch 23390 , basal ganglia , antagonist , pharmacology , neuroscience , chemistry , dopaminergic , psychology , receptor , medicine , biology , central nervous system
Cocaine stimulates locomotor activity by inhibiting the dopamine transporter (DAT) in nucleus accumbens (NAc) and dorsal striatum (dSTR) and thereby increasing extracellular dopamine (DA), which then binds to DA D1‐ and D2‐type receptors (D1Rs and D2Rs). Following an acute low dose of cocaine (10 mg/kg; ip), male Sprague‐Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on their drug‐induced locomotor activity. DATs and extracellular DA levels in LCRs and HCRs are differentially affected by acute cocaine, but whether D1Rs and D2Rs also differ has not been investigated. Here we used saturation binding of the D1R antagonist [3H]SCH 23390 to quantify D1Rs and the D2R antagonist [3H]raclopride to quantify D2Rs in NAc and dSTR at 40 min after acute cocaine. While the HCRs (N = 10) exhibited ~4‐fold greater cocaine‐induced locomotor activity than LCRs (N = 10) or saline controls (N = 7), there were no significant differences among the three groups in total numbers or affinities of D1Rs or D2Rs in either striatal region. Our results suggest that basal levels of striatal D1Rs and D2Rs are similar in LCRs and HCRs. However, our findings do not rule out the possibility that differences in D1R and/or D2R coupling/signaling, may help to explain the differential initial cocaine‐induced behavioral activation between LCRs and HCRs. Supported by DA004216 & DA015050.