Changes in Dopamine Neurotransmission in Rats with the Entorhinal Cortex Lesions.

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Following experiments were undertaken to investigate changes in dopamine (DA) neurotransmission associated with reduced excitatory amino acid transmission in the brain, especially in the entorhinal cortex where morphological abnormalities were reported in patients with schizophrenia. First, rats treated with antisense oligonucleotide complementary to mRNA of N-methyl-D aspartate (NMDA) R1 subunit, one of the subtypes of ionotropic glutamate receptors, were examined. In situ hybridization revealed that NMDA RI subunit mRNA expression was reduced in the periventricular structures such as the medial striatum and nucleus accumbens in the NMDA RI antisense-treated rats compared to the vehicle-treated rats. Variability in the firing pattern of A10 DA neurons was decreased in the antisense-treated rats.NMDA R1 antisense treatment induced no significant changes in mRNA expression levels of DA Dl and D2 receptors, and tyrosine hydroxylase. Further experiments are needed to investigate changes in DA D1 and D2 receptor binding using the receptor autoradiography. Second, rats with quinolinic acid lesions in the entorhinal cortex were examined. DA-related behaviors such as exploratory movements, metamphetamine-induced locomotor activity, and stereotypy are under investigation in the entorhinal- lesioned rats. Further experiments are also going on to quantify the receptor binding and mRNA expressions of DA receptors in cellular level in the entorhinal-lesioned rats.(CONTINUE TO NEXT PAGE)