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Region‐Specific Enhancement of Basal Extracellular and Cocaine‐Evoked Dopamine Levels Following Constitutive Deletion if tge Seritibub 1B Receptor
Author(s) -
Shippenberg T. S.,
Hen R.,
He M.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750258.x
Subject(s) - nucleus accumbens , dopamine , microdialysis , basal ganglia , medicine , endocrinology , striatum , serotonin , neurotransmitter , chemistry , biology , receptor , central nervous system
: The behavioral effects of cocaine are enhanced following constitutive deletion of the serotonin 1B receptor. The neural substrates mediating the enhanced response to cocaine are unknown. The present studies determined whether basal dopamine dynamics or cocaine‐evoked dopamine levels are altered in projection areas of mesostriatal or mesoaccumbens dopamine neurons following serotonin 1B receptor deletion. Male wild‐type and serotonin 1B knockout mice were implanted with microdialysis guide cannulas aimed at the dorsal striatum or nucleus accumbens. The zero net flux method of quantitative microdialysis was used to quantify basal extracellular dopamine concentrations (DA ext ) and the extraction fraction of dopamine ( E d ), which provides an index of dopamine uptake. Conventional microdialysis techniques were used to quantify cocaine (0, 5.0, and 20.0 mg/kg)‐evoked dopamine overflow. Basal DA ext and E d did not differ in striatum of wild‐type and knockout mice. Similarly, cocaine‐stimulated dopamine overflow did not differ between genotype. The basal E d did not differ in the nucleus accumbens of wild‐type and knockout mice. However, DA ext was significantly elevated in the nucleus accumbens of knockout mice. Cocaine‐evoked dopamine overflow (n M ) was also enhanced in the nucleus accumbens of knockout mice. However, the cocaine‐induced increase in dopamine levels, relative to basal values, did not differ between genotype. These data demonstrate that deletion of the serotonin 1B receptor is associated with increases in basal DA ext in the nucleus accumbens. This increase is not associated with an alteration in E d , suggesting increased basal dopamine release in these animals. It is hypothesized that these alterations in presynaptic neuronal activity are a compensatory response to constitutive deletion of the serotonin 1B receptor and may contribute to the enhanced behavioral effects of psychostimulants observed in knockout mice.