IN-VIVO ELECTROCHEMICAL MEASUREMENT OF THE LONG-LASTING RELEASE OF DOPAMINE AND SEROTONIN-INDUCED BY INTRASTRIATAL KAINIC ACID

Intrastriatal injection of the glutamate agonist kainic acid (KA) in r ats has been used to produce an animal model to investigate the mechan ism of acetylcholine and GABA cell death associated with Huntington's disease. In the present study, the time course of low (10(-5) M) and h igh (5 x 10(-3) M) concentrations of KA on striatal dopamine and serot onin release was studied in freely moving rats by using in vivo voltam metry. The response to low concentrations of KA varied between animals , either increasing dopamine release during the injection or increasin g dopamine and serotonin after the injection for an extended time, sug gesting that 10(-5) KA is near the threshold for KA toxicity in the st riatum in rats. High concentrations of KA suppressed dopamine release during injection, with both dopamine and serotonin release increasing and remaining elevated for 1-4 and 7-21 days, respectively. KA-induced changes were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione and bi cuculline increased the release of dopamine but not serotonin. These f indings suggest that KA-induced changes in dopamine release resulted f rom a disinhibition of dopamine neurons due to KA-mediated toxicity of striatal GABA neurons. An alternate possibility is that the change in dopamine and serotonin release may have arisen from a functional modi fication or degeneration of presynaptic terminals.