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

The effects of aniracetam on extracellular levels of dopamine (DA), seroton in (5-HT) and their metabolites were examined in five brain regions in free ly moving stroke-prone spontaneously hypertensive rats (SHRSP) using in viv o microdialysis. Basal DA release in SHRSP was uniformly lower in all regio ns tested than that in age-matched control Wistar Kyoto rats. 3,4-Dihydroxy phenylacetic acid and homovanillic acid levels were altered in the basolate ral amygdala, dorsal hippocampus and prefrontal cortex of SHRSP. While basa l 5-HT release decreased in the striatum and increased in the basolateral a mygdala, there was no associated change in 5-hydroxyindoleacetic acid level s. Systemic administration of aniracetam to SHRSP enhanced both DA and 5-HT release with partly associated change in their metabolite levels in the pr efrontal cortex, basolateral amygdala and dorsal hippocampus, but not in th e 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 metab olites (N-anisoyl-GABA and 2-pyrrolidinone) into the nucleus accumbens shel l produced no turning behavior. These findings indicate that SHRSP have a d opaminergic hypofunction throughout the brain and that aniracetam elicits a site-specific activation in mesocorticolimbic dopaminergic and serotonergi c pathways in SHRSP, possibly via nicotinic acetylcholine receptors in the ventral tegmental area and raphe nuclei. The physiological roles in the ani racetam-sensitive brain regions may closely link with their clinical effica cy towards emotional disturbances appearing after cerebral infarction. (C) 2001 Elsevier Science BN. All rights reserved.