4"12 E F F E C T O F B A C L O F E N ON T H E M E S O L I M B I C D O P A M I N E R G I C N E U R O N A L ACTIVITY ASSESSED W I T H D U A L - P R O B E B R A I N DIALYSIS .

M A S A M I YOSHIDA, HIDEYASU YOKOO, T A K A H I K O T A N A K A , K A T S U H I R O M I Z O G U C H I , H I R O Y U K I E M O T O A N D M A S A T O S H I T A N A K A , Depar tment o f Pharmacology, K u m m e Universi _ty School o f Medicine, Asahimachi 67, Kurume 830' Japar~.

l, nffision o f baclofen (10 "4M, 1 h) into the ventral tegmental area (VTA), the cell body site o f mesol imbic dopamine (DA) neuron sys tem in conscious rats, caused a decrease in both axonal and somatodendri t ic DA release in this neuron system, when assessed with brain dialysis using dual-probes placed in both the nucleus accumbens (NAC) and the VTA. Levels o f the metabolite of DA, 3,4-dihydroxyphenylacet ic acid (DOPAC) and homovanilliC acid (HVA) in the VTA decreases significantly in a similar manner fol lowing infusion of baclofen into the VTA, however, a pronounced increase in outf low of both D O P A C and H V A was seen in. dialisates f rom the NAC. Th isd i s soc ia ted response o f D A metabol i sm observed in the N A C is possibly derived f rom the autoregulatory mechanism located in the N A C - D A terminals.

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413 Dopamine DI receptor-mediated protection of kainate-induced cytotoxicity in rat striatal neurons. MASASHI SASA, TAKU AMANO, UJIHARA HISAMITSU*, HIROAKI MATSUBAYASHI, YUTAKA

TAMURA**, AKINORI AKAIKE**. Department of Pharmacology, Hiroshima University School of Medicine, Hiroshima 734, *Department of Pharmzrcolo~y, School of Medicine, Yama~uchi University, Ube 755, **Department of Neuropharmacolo~y, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama 729-02, Japan

We have previously reported that glutamate-induced cytotoxicity in primary cultured striatal cells is much less pronounced than cortical cells, and the cell death is protected by dopamine. This study was undertaken to elucidate the mechanism underlying the dopamine-induced protection of cytotoxicity in primary cultures of rat striatal neurons. On exposure to kainate (lmM) for 24 hr the cell viability of these cultured cells decreased in a dose-dependent manner. Dopamine at concentrations of 1-100pM dose-dependently reduced kainate- induced cytotoxicity. Protective effects of dopamine against kainate cytotoxicity were antagonized by SCH23390 (DI antagonist) but not domperidone (D2 antagonist). Moreover, kainate-induced cytotoxicity was prevented by SKF38393 (D1 agonist) but not by quinpirole (D2 agonist). In addition, stimultaneous treatment with dopamine and forskolin significantly enhanced the protective effects of dopamine alone. Patch clamp studies revealed that neither kaio.ate-induced currents nor NMDA-induced currents were affected by dopamine. These results suggest that dopanfine protects striatal neurons from kainate receptor-mediated cytotoxicity via D1 receptor activation with a subsequent increase in cAMP content.

414 DOPAMINERGIC INNERVATION OF THE MACAQUE CEREBRAL CORTEX : AN IMMUNOHISTOCHEMICAL STUDY.

TOSHIHIRO MAEDA17 KEIKO IKEMOTO 2) KEIJI SATOH 2

.Dep. of Anatomy l and Psychiatry 2, Shiga University of Medical Science~ Seta, Tsukinowa-cho, Otsu.JAPAN.

It is still controversial whether dopaminergic innervation of the cerebral cortex in the primate including human is restricted to just a few cortrical areas such as the prefrontal cortex as demonstrated in the rodent or not. The present study aimed to reveal the distribution of dopamine-immunoreactive (DA-IR) fibers and terminals of the cerebral cortex in Japanese monkey (Macaca fuscata). The cortical DA input in the monkey was considerably expanded compared with that in rodents.

DA-IR terminal fibers were distributed practically in all cortices, including sensory, rnbtor and assocication areas, to which dense innervation in layer I, the molecular layer, was common. Most rich innervation was found in the anterior cingulate and prefrontal cortices in which DA-IR varicose fibers were seen throughout all layers. The visual area (area 17) was most poorly innervated exclusively in layer I. These results may support that the dopamine system has a widespread role in cerebral cortical function, being involved in higher neural activity, in the primate.