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慢性ネコにおける脳幹圧迫による行動および脳波変化ならびにそれに対するthyrotropin-releasing hormone(TRH)の効果について検討した．脳幹圧迫は大槽を経て第4脳室内に挿入し，脳幹背面上に埋め込んだballoonを1～6分間膨脹させることにより行なった．脳幹圧迫開始10～36秒内にネコは横転し，四肢の痙性伸展位で不動状態となり，その後一部の例では軽度の前肢運動または頭部挙上などが途中において見られたが，全例45～120分後にようやく正常位に復した．大脳皮質脳波は圧迫開始初期の短時間の低振巾速波(脳波覚醒)につづき平坦波および棘波パターンとなり，その後直接あるいは脳波覚醒を経て高振巾徐波に移行した．これら脳幹圧迫による行動および脳波変化はTRHの静注により次の如く著明に改善された．すなわち，1mg/kg投与の12例中8例および0.5mg/kg投与の4例中1例は直ちに腹臥位または静踞位に復し，その後再度横転することはなかった．また，1mg/kg投与の3例および0.5mg/kg投与の2例において横転位のまま前肢の運動，struggling，頭部挙上あるいはrolling，軽度の位置移動の如き部分的回復が投与数分内に見られた．脳波は全例において用量依存的に持続的な覚醒波を惹起した．これらの結果は脳幹圧迫による意識障害様の行動および脳波の悪化状態に対してTRHが改善効果を有することを示す．

Thyrotropin-releasing hormone (TRH) and its analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate), significantly antagonized against reserpine-induced reduction of the spontaneous motor activity and the electroconvulsive threshold in mice. To search for sites of action and mechanisms, effects of DN-1417 on reserpine in local cerebral glucose utilization (LCGU) and cerebral monoamine levels were also investigated in rats. Reserpine (2 mg/kg, i.p., 24 hr pretreatment) reduced LCGU and the levels of cerebral monoamine in all the brain regions. DN-1417 (5 mg/kg, i.v.) significantly reversed the reduction of LCGU induced by reserpine in the thalamus dorsomedial nucleus, mamillary body, septal nucleus, caudate-putamen and nucleus accumbens. The effects of DN-1417 were completely abolished by pretreatment with a dopaminergic (DA) and a serotonergic (5-HT) receptor blocker, pimozide (1 mg/kg) and methysergide (5 mg/kg), respectively. DN-1417 (20 mg/kg, i.p.) reversed 5-HT level in the hypothalamus depleted by reserpine. These results suggest that the antagonistic effects of DN-1417 against reserpine-induced reduction of the locomotor activity and the electroconvulsive threshold seem to be mediated by DA- and 5-HT-ergic activations mainly in the nucleus accumbens and hypothalamus, respectively.

The effects of global cerebral ischemia on neurochemical parameters in the brain were examined in rats. Global cerebral ischemia was produced by temporary occlusion of the bilateral common carotid arteries 24 hr after the permanent electrocauterization of the bilateral vertebral arteries. In 10-min cerebral ischemic rats, the brain levels of monoamine were unaltered. The brain levels of gamma-aminobutyric acid (GABA), which increased about 1.5-fold just before recirculation, almost recovered to the levels of the sham operated group (sham ope. levels) within 5 min after recirculation. The brain levels of cyclic AMP (cAMP), although they altered a little just before recirculation, increased about 6-fold 1 min after recirculation, and they recovered to the sham ope. levels 3-5 min later. In 30-min cerebral ischemic rats, the brain levels of monoamine decreased to about 40% of the sham ope. levels just before recirculation, and norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels did not recover within 30 min after recirculation in the telencephalon. The brain GABA levels which increased about 2-fold just before recirculation, recovered to the sham ope. levels in all brain regions by 30-min recirculation except for the levels in cerebral cortex and cerebellum. The brain cAMP levels which increased about 3.5-fold 10 min after recirculation, almost recovered 20 min later. However, the cAMP levels in the telencephalon decreased to levels lower than the sham ope. levels 30 min after recirculation. It is suggested that the changes of these neurochemical parameters in the telencephalon are related in part to the abnormalities of behavior and EEG activity which have been already reported.

Effects of TRH and its analog, gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide citrate (DN-1417), on circling, stereotyped or climbing behavior were investigated in rats and mice. High doses of TRH (100 mg/kg, i.p.) and DN-1417 (20-50 mg/kg, i.p.) produced a significant ipsilateral circling behavior in rats with the lesions of the unilateral dopamine (DA) pathway by 6-hydroxydopamine. In intact mice, stereotyped sniffing accompanying hyperactivity was caused at low doses of TRH or DN-1417 (1-20 mg/kg, i.p.), and stereotyped licking behavior was observed at high doses of TRH or DN-1417 (20-200 mg/kg, i.p.). Furthermore, TRH, DN-1417 or methamphetamine caused a dose-related climbing behavior in mice pretreated with L-DOPA and Ro 4-4602. Circling behavior, stereotyped sniffing or licking behavior induced by TRH or DN-1417 was markedly suppressed by pretreatment with pimozide or alpha-methyltyrosine. However, atropine and scopolamine potentiated the circling inducing action of TRH or DN-1417, in contrast with suppression of the licking behavior. These results suggest that TRH and DN-1417 produce circling, sniffing, licking and climbing behaviors via activation of the central DA system, and that cholinergic mechanisms may be also involved in licking behavior induced by TRH or DN-1417.