Time course and regional specificity of neurochemical changes in the rat brain following intra-accumbal and intra-striatal injections of 6,7-ADTN (2-amino-6,7-dihydroxy-1,2,3-tetrahydronaphthalene)

Abstract

The dopaminergic theories used to explain the etiology of schizophrenia suggest that excessive dopaminergic transmission in major dopamine terminal areas leads to the positive and negative symptoms associated with the disease. More recently, serotonin has come to play a larger role in the drug therapy of schizophrenia. This experiment contains two different but conjoined studies that examine dopaminergic and serotonergic changes induced by a dopamine agonist. The first study examined the effects of 12.5 [mu]g of 6,7-ADTN bilaterally injected into the nucleus accumbens on neurochemical changes, specifically dopamine, HVA, DOPAC, serotonin and 5-HIAA, within the prefrontal cortex, nucleus accumbens, striatum, amygdala, substantia nigra, and ventral tegmental area. The second study examined the same neurochemical changes using the same time course within the same brain regions only following injections of ADTN into the striatum. This study found that neurochemical changes were not localized to only the sites of injection. Overall, after injection of 6,7 ADTN into the accumbens there was an increase in dopamine functional activity (DA/HVA ratio) in the amygdala and substantia nigra and an increase in dopamine turnover (DA/DOPAC ratio) in the amygdala. Increased serotonin had an inhibitory effect on dopamine in the prefrontal cortex and striatum. After injection of 6,7 ADTN into the striatum results showed an enormous increase in dopamine functional activity within the PFC that cannot be inhibited by the concomitant increase in serotonin. In conclusion, dopaminergic stimulation of the nucleus accumbens and striatum causes widespread and long term changes in their major afferent and efferent regions. --Résumé abrégé par UMI.