THYROTROPIN-RELEASING-HORMONE - HYPERACTIVITY AND MESOLIMBIC DOPAMINE SYSTEM IN RATS

被引:60
作者
MIYAMOTO, M
NARUMI, S
NAGAI, Y
SHIMA, T
NAGAWA, Y
机构
[1] TAKEDA CHEM IND LTD, BIOL RES LABS, OSAKA 532, JAPAN
[2] TAKEDA CHEM IND LTD, DIV CENT RES, CHEM RES LABS, OSAKA 532, JAPAN
关键词
D O I
10.1254/jjp.29.335
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The mechanism of stimulatory action of thyrotropin-releasing hormone (TRH) on spontaneous motor activity was investigated in rats. TRH produced a significant hyperactivity with intraperitoneal administration of 20 mg/kg or bilateral injection of 10 μg into the nucleus accumbens septi (NAS). Following bilateral injection of 6-hydroxydopamine into the mesolimbic dopamine (DA) pathway, the hyperactivity induced by TRH was not altered, whereas the response to apomorphine given intraperitoneally or DA injected into the NAS was clearly enhanced. The TRH-induced hyperactivity was remarkably suppressed by α-methyltyrosine and in contrast, augmented by pargyline. Systemic injection of aminooxyacetic acid in a dose producing behavioral depression reduced markedly the TRH-induced hyperactivity. Bilateral injection of ethanolamine 0-sulphate (100 μg) into the NAS produced no behavioral depression per se, but remarkably attenuated the hyperactivity response to TRH or DA (20 μg) given intraperitoneally or into the NAS. Both TRH (10-5 and 10-4 M) and methamphetamine (10-6-10-4 M) increased the spontaneous release of 14C-DA from rat NAS slices. These findings suggest that TRH induces hyperactivity by enhancing DA release from nerve terminals in the NAS without a direct stimulation of the post-synaptic DA receptors. TRH and GABA, independently or via interaction between them, may play a reciprocal regulatory role in the activity of the mesolimbic DA system. © 1979, The Japanese Pharmacological Society. All rights reserved.
引用
收藏
页码:335 / 347
页数:13
相关论文
共 35 条
[1]  
ANDEN NE, 1977, ACTA PHARMACOL TOX, V40, P310
[2]   REGIONAL GAMMA-AMINOBUTYRIC ACID LEVELS IN RAT-BRAIN DETERMINED AFTER MICROWAVE FIXATION [J].
BALCOM, GJ ;
LENOX, RH ;
MEYERHOFF, JL .
JOURNAL OF NEUROCHEMISTRY, 1975, 24 (04) :609-613
[3]  
BREESE GR, 1975, J PHARMACOL EXP THER, V193, P11
[4]   STEREOTYPED BEHAVIOR PATTERNS AND HYPERACTIVITY INDUCED BY AMPHETAMINE AND APOMORPHINE AFTER DISCRETE 6-HYDROXYDOPAMINE LESIONS OF EXTRAPYRAMIDAL AND MESOLIMBIC NUCLEI [J].
COSTALL, B ;
MARSDEN, CD ;
NAYLOR, RJ ;
PYCOCK, CJ .
BRAIN RESEARCH, 1977, 123 (01) :89-111
[5]   ANTAGONISM OF ANALEPTIC ACTIVITY OF THYROTROPIN-RELEASING-HORMONE (TRH) BY AGENTS WHICH ENHANCE GABA TRANSMISSION [J].
COTT, J ;
ENGEL, J .
PSYCHOPHARMACOLOGY, 1977, 52 (02) :145-149
[6]  
DEGROOT J, 1959, VERH K NED AKAD WET, V52, P1
[7]   BRAIN GABA, DOPAMINE AND ACETYLCHOLINE INTERACTIONS .1. STUDIES WITH OXOTREMORINE [J].
DELAMORA, MP ;
FUXE, K .
BRAIN RESEARCH, 1977, 135 (01) :107-122
[8]   ORIGIN AND DISTRIBUTION OF GLUTAMATE DECARBOXYLASE IN SUBSTANTIA NIGRA OF CAT [J].
FONNUM, F ;
GROFOVA, I ;
RINVIK, E ;
STORMMAT.J ;
WALBERG, F .
BRAIN RESEARCH, 1974, 71 (01) :77-92
[9]   ANALYSIS OF MAJOR AMINO-ACIDS OF RAT-BRAIN AFTER IN-VIVO INHIBITION OF GABA TRANSAMINASE BY ETHANOLAMINE O-SULFATE [J].
FOWLER, LJ .
JOURNAL OF NEUROCHEMISTRY, 1973, 21 (02) :437-440
[10]  
FUXE K, 1975, MED BIOL, V53, P177