Lesion of caudate-putamen interneurons with kainic acid alters dopamine and serotonin metabolism in the olfactory tubercle of the rat.
1. The existence of functional interrelationships between dorsal and ventral regions of the rat striatum was investigated. Kainic acid (KA) was employed to induce neuronal lesions in the more dorsal striatum, the caudate-putamen (CP). Only one CP (one side) received KA. KA-induced neurotoxicity at the site of injection (CP) was evidenced by reductions in choline-acetyltransferase activity and in GABA levels, and by increases in the ratios metabolite/monoamine for dopamine (DA) and serotonin (5-HT). 2. In addition to the well-known local effects, direct stereotaxic injection of KA into the CP produced distant effects in the ipsilateral olfactory tubercle (OT). A dose-dependent increase in the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) and decreases in DA and 5-HT concentrations were observed in the OT ipsilateral to the CP injected with KA. With 1, 2, 3, and 4 microg of KA, the ratio DOPAC+HVA/DA in the OT was 30, 79, 140, and 173% higher, respectively, than control levels. With 2, 3, and 4 microg of KA, the levels of 5-HIAA were approximately 30, 60, and 120% higher than control values, and the changes in 5-HIAA were associated with significant reductions in 5-HT concentrations. 3. Our results suggest that the dorsal part of the striatum exerts important regulatory functions over the most ventral striatal region, the OT. Destruction of CP interneurons by KA leads to disinhibition of DA and 5-HT activities to the OT. The functional interactions between dorsal and ventral striatal regions may play a role in the integration of fundamental life-preserving, motivational, and goal-directed olfactory motor behaviors of rodents.
Guevara
Beatriz H
BH
Neuropharmacology Unit, Department of Pharmacology, School of Pharmacy, Central University of Venezuela, Caracas, Venezuela.
Torrico
Fátima
F
Hoffmann
Irene S
IS
Cubeddu
Luigi X
LX
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007608:Kainic Acid / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009498:Neurotoxins / Q000494:pharmacology; D009833:Olfactory Pathways / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*
D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D007608:Kainic Acid; D004298:Dopamine; D006719:Homovanillic Acid