Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdialysis.
This study examined the acute effects of the novel antidepressant drug, bupropion, on extracellular concentrations of dopamine (DA), its metabolites, and the serotonin metabolite 5-HIAA in the striatum and nucleus accumbens using on-line microdialysis in freely moving rats. Bupropion HCl (10, 25, and 100 mg/kg intraperitoneally) increased extracellular striatal DA in a dose- and time-dependent manner; 1 mg/kg did not affect extracellular DA. The maximal response occurred within the first 20 minutes (+76%, +164%, and +443% for each dose, respectively) followed by a gradual decrease to a stable but elevated level for the next 2 hours. This neurochemical response was strongly associated with bupropion-induced stereotyped behavior during the first hour but not during the subsequent 2 hours. Bupropion decreased DOPAC concentrations, increased 5-HIAA, and had variable effects on homovanillic acid (HVA) (decreases with 10 mg/kg and increases with 25 and 100 mg/kg). The increase in extracellular DA after bupropion (25 mg/kg) was blocked by tetrodotoxin and was therefore action-potential-dependent. Bupropion produced similar neurochemical responses in the striatum and the nucleus accumbens. These results suggest that increases in DA transmission contribute to the behavioral effects of bupropion and are consistent with a role for DA in the antidepressant effects of this drug. The partial dissociation between DA release and stereotyped behavior suggests that the relationship between neurotransmitter release and behavior may be complex.
Nomikos
G G
GG
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Damsma
G
G
Wenkstern
D
D
Fibiger
H C
HC
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D016642:Bupropion; D003342:Corpus Striatum / Q000378:metabolism*; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000378:metabolism*; D011427:Propiophenones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012686:Septal Nuclei / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects
D000928:Antidepressive Agents; D011427:Propiophenones; D016642:Bupropion; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid