In vivo effects of aripiprazole on cortical and striatal dopaminergic and serotonergic function.
In vivo microdialysis was used to monitor the effects of oral aripiprazole and olanzapine on basal extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) in the medial prefrontal cortex and striatum of conscious, freely moving rats. Acute aripiprazole administration did not affect dopamine output, but produced moderate increases in DOPAC and HVA concentrations, in medial prefrontal cortex or striatum of drug-naïve rats. Similarly, aripiprazole did not affect dopamine output but produced moderate elevations in DOPAC and HVA concentrations in the striatum of chronic aripiprazole-pretreated rats. Olanzapine produced comparatively larger elevations in dopamine, DOPAC, and HVA in both regions, which, in the striatum, were diminished after chronic olanzapine exposure. Aripiprazole reduced extracellular 5-HIAA concentrations in the medial prefrontal cortex and striatum of drug-nai;ve rats, but not in chronic aripiprazole-pretreated rats. Together, these data provide in vivo evidence of aripiprazole-induced changes in forebrain dopaminergic and serotonergic function that may reflect its partial agonist activity at presynaptic dopamine D(2) and 5-HT(1A) receptors and antagonist activity at 5-HT(2A) receptors.
Jordan
Shaun
S
Neuroscience Department, Maryland Research Laboratories, Otsuka Maryland Research Institute, 9900 Medical Center Drive, Rockville, MD 20850, USA. shaunj@otsuka.com
Koprivica
Vuk
V
Dunn
Robert
R
Tottori
Katsura
K
Kikuchi
Tetsuro
T
Altar
C Anthony
CA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D015102:3,4-Dihydroxyphenylacetic Acid; D014150:Antipsychotic Agents; D000068180:Aripiprazole; D001569:Benzodiazepines; D004298:Dopamine; D006719:Homovanillic Acid; D006897:Hydroxyindoleacetic Acid; D000077152:Olanzapine; D010879:Piperazines; D015363:Quinolones; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors