Site-specific activation of dopamine and serotonin transmission by aniracetam in the mesocorticolimbic pathway of rats

Brain Res. 2001 Apr 6;897(1-2):82-92. doi: 10.1016/s0006-8993(01)02096-0.


The effects of aniracetam on extracellular levels of dopamine (DA), serotonin (5-HT) and their metabolites were examined in five brain regions in freely moving stroke-prone spontaneously hypertensive rats (SHRSP) using in vivo microdialysis. Basal DA release in SHRSP was uniformly lower in all regions tested than that in age-matched control Wistar Kyoto rats. 3,4-Dihydroxyphenylacetic acid and homovanillic acid levels were altered in the basolateral amygdala, dorsal hippocampus and prefrontal cortex of SHRSP. While basal 5-HT release decreased in the striatum and increased in the basolateral amygdala, there was no associated change in 5-hydroxyindoleacetic acid levels. Systemic administration of aniracetam to SHRSP enhanced both DA and 5-HT release with partly associated change in their metabolite levels in the prefrontal cortex, basolateral amygdala and dorsal hippocampus, but not in the striatum and nucleus accumbens shell, in a dose-dependent manner (30 and/or 100 mg/kg p.o.). Microinjection (1 and 10 ng) of aniracetam or its metabolites (N-anisoyl-GABA and 2-pyrrolidinone) into the nucleus accumbens shell produced no turning behavior. These findings indicate that SHRSP have a dopaminergic hypofunction throughout the brain and that aniracetam elicits a site-specific activation in mesocorticolimbic dopaminergic and serotonergic pathways in SHRSP, possibly via nicotinic acetylcholine receptors in the ventral tegmental area and raphe nuclei. The physiological roles in the aniracetam-sensitive brain regions may closely link with their clinical efficacy towards emotional disturbances appearing after cerebral infarction.

MeSH terms

  • Amygdala / cytology
  • Amygdala / metabolism
  • Animals
  • Behavior, Animal / drug effects
  • Dopamine / metabolism*
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Male
  • Microdialysis
  • Motor Activity / drug effects
  • Neural Pathways / metabolism
  • Nootropic Agents / pharmacology*
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / metabolism
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / metabolism
  • Prosencephalon / cytology
  • Prosencephalon / metabolism*
  • Pyrrolidinones / pharmacology*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Serotonin / metabolism*
  • Stroke / drug therapy
  • Stroke / metabolism
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology


  • Nootropic Agents
  • Pyrrolidinones
  • Serotonin
  • aniracetam
  • Dopamine