Kazunobu Sugawara

Potentiating effect of lithium chloride on aggressive behaviour induced in mice by nialamide plus L-DOPA and by clonidine

Effects of acute administration of LiCl on aggressive behavior and alterations in brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) contents induced by nialamide plus L-DOPA and by clonidine were examined in mice. Effects of LiCl on turnover and metabolism of brain NE were also investigated. LiCl potentiated the aggressiveness induced by both nialamide plus L-DOPA and by clonidine. Increase in levels of brain NE, DA and 5-HT by nialamide plus L-DOPA was not affected by LiCl. The potentiating effect of LiCl on clonidine aggression was not observed in mice pretreated with disulfiram. Although LiCl did not alter the steady state levels of brain NE, DA and 5-HT, it increased the turnover of NE and decreased the content of endogenous normetanephrine. These results favour the assumption that lithium reduces the ability of nerve terminal vesicles to store NE leading to an increased turnover and decreased concentration of NE at receptor sites.

Sensitivity of the isolated vas deferens of the guinea-pig to norepinephrine and acetylcholine after denervation, decentralization and treatments by various agents

Abstract The sensitivity of the isolated vas deferens of the guinea-pig to norepinephrine (NE) and acetylcholine (ACh) after various treatments was examined and the following results were obtained. The sensitivity of the isolated vas deferens to NE was markedly increased at 2, 7 and 28 days after denervation and by cocaine 10 −6 M or hexylguanidine 10 −4 M. It was moderately increased by long-term treatment with reserpine (0.1 mg/kg/day for 7–14 days) or guanethidine (10 mg/kg/day for 7 days). Supersensitivity after denervation appeared after 2 days and reached a maximum about 7 days after operation. The onset of supersensitivity after denervation was more rapid than after cocaine or hexylguanidine. The sensitivity to NE was decreased by treatment with tetrodotoxin (0.5–2 μg/kg/day for 14–28 days) or by cold storage (6–8°C, for 7 days). Sensitivity to NE was not affected 7 and 28 days after decentralization or by short-term treatment with reserpine (3 mg/kg, 24 hr prior to experiment, 1 mg/kg/day for 2 days), hexamethonium (2–5 mg/kg/day, twice daily) or tetrodotoxin (0.1–2 gmg/kg/day for 7 days). Cocaine increased supersensitivity after denervation and after cold storage. The sensitivity of the isolated vas deferens to ACh was not changed by any of the afore mentioned treatments and procedures except for cold storage. It is concluded that the supersensitivity of the guinea-pig isolated vas deferens after various treatments is specific for NE, and that the supersensitivity is mainly due to the impairment of NE uptake into the adrenergic nerve endings, but a postsynaptic mechanism cannot be excluded.

General Pharmacological Actions of N-Acetoacetyl-3-hydroxytyrosine

The general pharmacological actions of N-acetoacetyl-3-hydroxytyrosine (L-DOPA acetoacetate) were investigated and compared with those of L-3, 4-dihydroxypenylalanine (L-DOPA). The following results were obtained. 1) L-DOPA acetoacetate and L-DOPA suppressed slightly the spontaneous motor activity in mice. 2) L-DOPA acetoacetate and L-DOPA showed no effect on the sleeping time induced by hexobarbital and on maximal electroshock-, pentetrazol- and strychnine-convulsions in mice, but maximal electroshock convulsion was inhibited by the combined administration of L-DOPA and a monoamine oxidase inhibitor, pargyline. 3) L-DOPA acetoacetate and L-DOPA suppressed the squirming induced by acetic acid in mice. 4) L-DOPA acetoacetate did not have a hypothermic action in mice although L-DOPA did slightly. 5) In anaesthetized rats, L-DOPA acetoacetate and L-DOPA produced a slight temporary rise in the blood pressure and potentiated the pressor actions of norepinephrine and tyramine. The tyramine-induced tachyphylaxis and the abolishment of the response of tyramine induced with reserpine pretreatment were restored by both compounds. 6) On the isolated smooth muscle preparations such as guinea-pig vas deferens, intestine, aorta, rabbit aorta and rat uterus, the contractions induced by several agonists were almost unaffected by L-DOPA acetoacetate and L-DOPA. On guinea-pig vas deferens, aorta and rabbit aorta preparations, however, the tyramine-induced tachyphylaxis and the abolishment of the response of tyramine induced with reserpine pretreatment were restored by both compounds. These restorations were not observed by the treatment of a peripheral DOPA decarboxylase inhibitor, Ro4-4602. These actions were also found on guinea-pig atria preparations. Furthermore, on rat uterus preparations, both compounds increased the spontaneous motility. 7) On the gastrointestinal propulsion in mice and on the isolated skeletal muscle preparations in frog, L-DOPA acetoacetate and L-DOPA showed no effect. From the results mentioned above, it could be assumed that L-DOPA acetoacetate possessed only peripheral without central action though L-DOPA possessed both of central and peripheral actions, and that the activities would be due to their metabolites.