Premium
Individual differences to cocaine activation and self‐administration in rats: role of the brain dopamine transporter
Author(s) -
Zahniser Nancy R,
Mandt Bruce H,
Schenk Susan,
Allen Richard M
Publication year - 2008
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.22.1_supplement.533.2
Subject(s) - dopamine transporter , dopamine , addiction , cocaine abuse , conditioned place preference , dopamine uptake inhibitors , psychology , self administration , locomotor activity , pharmacology , brain stimulation reward , transporter , sensitization , differential effects , cocaine dependence , behavioral sensitization , neuroscience , medicine , dopaminergic , psychiatry , biology , nucleus accumbens , biochemistry , gene
Individuals differ in their responsiveness to psychostimulants like cocaine, which produce their activating effects largely by inhibiting the dopamine transporter (DAT). This differential responsiveness may impact subsequent drug abuse and addiction. Adult outbred Sprague‐Dawley rats also differ in their responsiveness to cocaine and can be classified as either low or high cocaine responders (LCRs or HCRs), based on the magnitude of each rat's locomotor activity resulting from its first exposure to low dose cocaine. Initially, cocaine inhibits striatal DAT activity only in HCRs; and LCR/HCR differences in rapid cocaine‐induced regulation of DATs parallel their behavioral differences. With repeated daily cocaine administration, however, cocaine begins to inhibit striatal DAT activity in LCRs. Also with repeated cocaine, LCRs more readily develop behaviors associated with enhanced drug responsiveness and reward than HCRs: viz. cocaine‐induced locomotor sensitization, conditioned place preference and greater motivation to self‐administer cocaine. Together, our findings suggest that the initial responsiveness of striatal DATs to cocaine helps to explain the variable locomotor activation to cocaine and may also contribute to the differential reinforcing effectiveness of cocaine in individuals. Supported by NIH grants DA004216, DA015050, DA023343.