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1903 Behavioral and neurochemical evidences that w-conotoxin gvia inhibits the striatal dopamine release in vivo
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903
B E H A V I O R A L AND N E U R O C H E M I C A L E V I D E N C E S T H A T W - C O N O T O X I N G V I A I N H I B I T S THE S T R I A T A L D O P A M I N E R E L E A S E IN VIVO. KIYQFUM I Y A M A D A ~, TOMOMI T E R A Q K A 2, SEIJI M O R I T A 2, T A K A A K I H A S E G A W A ~ AND T Q S H I T A K ~ NABESHIMA* IDcpt. of N e u r o n s v c h o n h a r m a c o l . and Hosp. Pharm., N a g o y a Univ. Sch, O [ Med., N a g o y a 466, Japan and ~Third T o k u s h i m a Inst. of N e w D r u a Res., O t s u k a pharmac=_. Co., Ltd., T o k u s h i m a 771-01, J a p a n The b e h a v i o r a l and n e u r o c h e m i c a l e f f e c t s of w - c o n o t o x i n (w-CTX) w e r e e x a m i n e d to c l a r i f y the i n v o l v e m e n t of N - t y p e voltage s e n s i t i v e c a l c i u m c h a n n e l s (N-channels) in the s t r i a t a l d o p a m i n e (DA) r e l e a s e in vivo. Intracerebroventricular injection of w-CTX or neomycin, b o t h N - c h a n n e l antagonists, c a u s e d a d o s e - d e p e n d e n t i n h i b i t i o n of methylphenidate-induced hypermotility in mice, but failed to inhibit methamphetamine-induced hyperactivity. W - C T X also i n h i b i t e d the c i r c l i n g b e h a v i o r induced by m e t h y l p h e n i d a t e in rat that had k a i n i c a c i d - i n d u c e d u n i l a t e r a l s t r i a t a l lesion. When w - C T X was injected directly into the rat striatum, it c a u s e d a d o s e - d e p e n d e n t r e d u c t i o n of the ratios of 3 , 4 - d i h y d r o x y p h e n y l a c e t i c a c i d (DOPAC)/DA and h o m o v a n i l l i c acid (HVA)/DA. These results suggest that N - c h a n n e l s mediate c a l c i u m i n f l u x into n e r v e t e r m i n a l s in rive, this c a l c i u m i n f l u x b e i n g c r u c i a l for striatal D A release.
1904
Hypothalamic histamine modulates physiological responses induced by circulating interleukin-l~. MASAHIRO KANG, H I R O N O B U YOSHIHATSU, MAHORU KUROKAWA, YUICHI TAHARI, RYUICHI OGAWA, MARI T A T S U K A W A AND T O S H I I E SAKATA, D e p a r t m e n t . of I n t e r n a l M e d i c i n e I, O i t a M e d i c a l U n i v e r s i t y . We c l a r i f i e d the i n v o l v e m e n t of h y p o t h a l a m i c histamine (HA) in p h y s i o l o g i c a l responses induced by circulating interleukin-l~ (IL-I~). D e p l e t i o n of n e u r o n a l HA i n d u c e d ~ y i n t r a p e r i t o n e a l (in) i n j e c t i o n of a - f l u o r o m e t h y l h ! s t i d i n e (FMH), a suicide i n h i b i t o r of H A s y n t h e s i z i n g emzyme histidine decarboxylase (HDC), attenuated feeding suppression (p
I 905
SELF-~TILATION BEHAVIOR AND BRAIN DOPAHINE IN NEONATAL 6-HYDROXYDOP~MINE RATS. 3 RECEPTOR BINDINGS AND IN SITU HYBRIDIZATION OF DOP~MINE DI RECEPTOR.
TREATED CHIHIRO
~ I , HITOSHI OKAMURA 2 AND YASUHIKO IBATA2 , Department of 1 P s y c h i a t r y and 2 Anatomy, KyotO YOKOY~ P r e f e c t u r a l U n i v e r s i t y of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602, Japan.
Rats r e c e i v e d with i n t r a c i s t e r n a l 6-hydroxydopamine (6-OHDA) i n j e c t i o n a t n e o n a t a l age have permanent dopamine (DA) d e p l e t i o n i n t h e i r b r a i n s , and show b e h a v i o r a l DA h y p e r s e n s i t i v i t y a t a d u l t age, such as s e l f - m u t i l a t i o n b e h a v i o r (SHB) a f t e r loading of L-DOPA. SMB could be mainly mediated by D1 r e c e p t o r , because D1 sp%cific s g o n l s t s and a n t a g o n i s t s d i r e c t l y cause induction
and supression of SMB, respectively. In this study, we investigated dopamine DI receptor binding activity and mRNA expression in the 6-OHDA treated rats showing SMB (=SMB(+) group) not showing SHB (=SMB(-) group), and the saline treated ra~s (=control group), by quantitive in vitro receptor autoradiography and binding assay using [ H]SCH 23390, and in situ hybridization u~ing [~ S]labeled DI oligonucleotide probe. In autonadiographic binding analysis of [ H]SCH23390, the binding densities in the caudate-p~tamen(CP), the nucleus accumbens(Aeb) and the tuberculum olfactorium(TuO) were not different among three groups. The binding density in the substantia nigra pars retieulata(SNR) was increased in SMB(+) compared with SMB(-~ and control(p<0.05). In binding assay using the homogenate of nigral tissue, Bmax value of [~H]SCH 23390 binding was increased in SMB(+) compared with £hat of SMB(-) and control, while Kd value was net changed. The signals of D1 mRN~ by'X-ray film analysis of in. situ hybridization in CP, Aeb and TuO did not show prominent difference among three groups. The present study has revealed that SNR was the only area where D1 binding was increased in SHB(+) group. It suggests that DI receptor in SNR might play an important role for SMB, but the increase of the number of D1 receptor is not accompanied with the alternation of DI mRNA in the striatum.
903
B E H A V I O R A L AND N E U R O C H E M I C A L E V I D E N C E S T H A T W - C O N O T O X I N G V I A I N H I B I T S THE S T R I A T A L D O P A M I N E R E L E A S E IN VIVO. KIYQFUM I Y A M A D A ~, TOMOMI T E R A Q K A 2, SEIJI M O R I T A 2, T A K A A K I H A S E G A W A ~ AND T Q S H I T A K ~ NABESHIMA* IDcpt. of N e u r o n s v c h o n h a r m a c o l . and Hosp. Pharm., N a g o y a Univ. Sch, O [ Med., N a g o y a 466, Japan and ~Third T o k u s h i m a Inst. of N e w D r u a Res., O t s u k a pharmac=_. Co., Ltd., T o k u s h i m a 771-01, J a p a n The b e h a v i o r a l and n e u r o c h e m i c a l e f f e c t s of w - c o n o t o x i n (w-CTX) w e r e e x a m i n e d to c l a r i f y the i n v o l v e m e n t of N - t y p e voltage s e n s i t i v e c a l c i u m c h a n n e l s (N-channels) in the s t r i a t a l d o p a m i n e (DA) r e l e a s e in vivo. Intracerebroventricular injection of w-CTX or neomycin, b o t h N - c h a n n e l antagonists, c a u s e d a d o s e - d e p e n d e n t i n h i b i t i o n of methylphenidate-induced hypermotility in mice, but failed to inhibit methamphetamine-induced hyperactivity. W - C T X also i n h i b i t e d the c i r c l i n g b e h a v i o r induced by m e t h y l p h e n i d a t e in rat that had k a i n i c a c i d - i n d u c e d u n i l a t e r a l s t r i a t a l lesion. When w - C T X was injected directly into the rat striatum, it c a u s e d a d o s e - d e p e n d e n t r e d u c t i o n of the ratios of 3 , 4 - d i h y d r o x y p h e n y l a c e t i c a c i d (DOPAC)/DA and h o m o v a n i l l i c acid (HVA)/DA. These results suggest that N - c h a n n e l s mediate c a l c i u m i n f l u x into n e r v e t e r m i n a l s in rive, this c a l c i u m i n f l u x b e i n g c r u c i a l for striatal D A release.
1904
Hypothalamic histamine modulates physiological responses induced by circulating interleukin-l~. MASAHIRO KANG, H I R O N O B U YOSHIHATSU, MAHORU KUROKAWA, YUICHI TAHARI, RYUICHI OGAWA, MARI T A T S U K A W A AND T O S H I I E SAKATA, D e p a r t m e n t . of I n t e r n a l M e d i c i n e I, O i t a M e d i c a l U n i v e r s i t y . We c l a r i f i e d the i n v o l v e m e n t of h y p o t h a l a m i c histamine (HA) in p h y s i o l o g i c a l responses induced by circulating interleukin-l~ (IL-I~). D e p l e t i o n of n e u r o n a l HA i n d u c e d ~ y i n t r a p e r i t o n e a l (in) i n j e c t i o n of a - f l u o r o m e t h y l h ! s t i d i n e (FMH), a suicide i n h i b i t o r of H A s y n t h e s i z i n g emzyme histidine decarboxylase (HDC), attenuated feeding suppression (p
I 905
SELF-~TILATION BEHAVIOR AND BRAIN DOPAHINE IN NEONATAL 6-HYDROXYDOP~MINE RATS. 3 RECEPTOR BINDINGS AND IN SITU HYBRIDIZATION OF DOP~MINE DI RECEPTOR.
TREATED CHIHIRO
~ I , HITOSHI OKAMURA 2 AND YASUHIKO IBATA2 , Department of 1 P s y c h i a t r y and 2 Anatomy, KyotO YOKOY~ P r e f e c t u r a l U n i v e r s i t y of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602, Japan.
Rats r e c e i v e d with i n t r a c i s t e r n a l 6-hydroxydopamine (6-OHDA) i n j e c t i o n a t n e o n a t a l age have permanent dopamine (DA) d e p l e t i o n i n t h e i r b r a i n s , and show b e h a v i o r a l DA h y p e r s e n s i t i v i t y a t a d u l t age, such as s e l f - m u t i l a t i o n b e h a v i o r (SHB) a f t e r loading of L-DOPA. SMB could be mainly mediated by D1 r e c e p t o r , because D1 sp%cific s g o n l s t s and a n t a g o n i s t s d i r e c t l y cause induction
and supression of SMB, respectively. In this study, we investigated dopamine DI receptor binding activity and mRNA expression in the 6-OHDA treated rats showing SMB (=SMB(+) group) not showing SHB (=SMB(-) group), and the saline treated ra~s (=control group), by quantitive in vitro receptor autoradiography and binding assay using [ H]SCH 23390, and in situ hybridization u~ing [~ S]labeled DI oligonucleotide probe. In autonadiographic binding analysis of [ H]SCH23390, the binding densities in the caudate-p~tamen(CP), the nucleus accumbens(Aeb) and the tuberculum olfactorium(TuO) were not different among three groups. The binding density in the substantia nigra pars retieulata(SNR) was increased in SMB(+) compared with SMB(-~ and control(p<0.05). In binding assay using the homogenate of nigral tissue, Bmax value of [~H]SCH 23390 binding was increased in SMB(+) compared with £hat of SMB(-) and control, while Kd value was net changed. The signals of D1 mRN~ by'X-ray film analysis of in. situ hybridization in CP, Aeb and TuO did not show prominent difference among three groups. The present study has revealed that SNR was the only area where D1 binding was increased in SHB(+) group. It suggests that DI receptor in SNR might play an important role for SMB, but the increase of the number of D1 receptor is not accompanied with the alternation of DI mRNA in the striatum.