一种白僵菌代谢产物提取物对利血平拮抗实验的影响

目的研究一种白僵菌代谢产物提取物 (BCEF)对利血平拮抗实验的影响。方法采用预防性一次灌胃给药、预防性连续灌胃给药、治疗性连续灌胃给药观察BCEF对利血平拮抗实验的影响。结果皮下注射 (sc)利血平后动物呈现利血平化 :出现眼睑下垂、体温下降及活动抑制。小鼠、大鼠BCEF2 5、5 0、10 0mg·kg-1预防性一次灌胃对利血平 (sc ,2、2 .5mg·kg-1,qd× 1d)、大鼠BCEF2 5、5 0、10 0mg·kg-1预防性连续灌胃 14d ,对利血平 (sc ,2 .5mg·kg-1,qd× 1d)致上睑下垂及活动抑制均无明显改变 ;小鼠BCEF5 0、10 0mg·kg-1治疗性连续灌胃 14天 ,可明显改善利血平 (sc ,0 .2mg·kg-1,qd× 14d)化小鼠的眼睑下垂及活动抑制。结论BCEF对利血平拮抗实验具有一定的改善作用。提示BCEF具有部分增强单胺递质系统的作用。     

丁螺环酮加强戊四氮致小鼠惊厥作用

新型非苯二氮(艹卓)类抗焦虑剂丁螺环酮(Bus)(1～10 mg·kg~1)使戊四氮(PTZ)致惊厥作用的CD_(50)下降12～37％,具有剂量依赖性和时间效应关系.色氨酸羟化酶抑制剂对氯苯丙氨酸(250 mg·kg~1)和单胺耗竭剂利血平(2mg·kg~1)均可增强PTZ致惊厥作用,但同时减弱Bus的增强作用.而α_2受体激动剂可乐定和赛拉嗪以及DA受体激动剂阿朴吗啡,拮抗剂氟哌啶醇均不影响Bus的增强作用.结果表明,Bus的增强作用有5-HT能神经元的参与.     

Effects of extended periods of reserpine and α-methyl-p-tyrosine treatment on the development of the putamen in fetal rabbits

Developing nigrostriatal neuroblasts exhibit catecholamine-induced fluorescence before their axons have left the vicinity of the cell bodies. To evaluate possible developmental effects of dopamine, we have used reserpine and α-methyl-p-tyrosine to deplete dopamine chronically during the development of these axons. We found that dopamine-induced fluorescence was either absent or markedly decreased in the fetal putamens. To determine whether the absence of fluorescence was due to a reduction of dopamine terminals, the uptake of tritium-labeled dopamine was measured in the putamen. Uptake of labeled dopamine was significantly depressed in reserpine-treated fetuses to 70% of that of controls; however, no depression of labeled dopamine was found in the α-methyl-p-tyrosine-treated fetuses. After both drug treatments, the striatal perikarya were less mature than those of controls. Although we cannot rule out possible non-specific or toxic effects of the drugs, these observations support the conclusion that presynaptic dopamine may be important for development of target neurons in the neostriatum.     

The effect of immunosympathectomy on the responses of the mouse to reserpine and various

The technique of immunosympathectomy was used to investigate the relative importance of sympathetically mediated processes in the body temperature responses of mice to reserpine treatment and the thermogenic effects of subsequently administered anti-depressant and CNS stimulant drugs.It was found that immunosympathectomized mice were less sensitive to the temperature lowering effects of reserpine but exhibited, unexpectedly, an enhanced thermogenic response to each of the representative antidepressant and stimulant drugs tested.These findings appear to exclude the sympathetic division of the autonomic nervous system as an essential prerequisite for the thermogenic effects of anti-depressant and stimulant drugs in reserpine treated mice. It is suggested that the observed effects could be accounted for in terms of a possible hyperfunctional adrenal gland.The findings reported above were presented, in part, at the 7th International Congress of C.I.N.P., Prague, Czechoslovakia, August 1970.     

Muscarinic receptor regulation in the sympathetically innervated avian expansor secundariorum

We sought to examine further the regulation of muscarinic receptors in the developing expansor secundariorum, a smooth muscle of the avian wing. [³H]Quinuclidinyl benzilate binding was used as a measure of muscarinic receptors present in the muscle, which gradually decline in density from hatch during the following few weeks. Receptor loss can be prevented by denervation of the muscle immediately after hatch, but receptor density is not recovered by denervation in older birds. As the major innervation is provided by sympathetic, noradrenergic fibres with no evidence of a cholinergic input, the action of several pharmacological agents known to affect noradrenergic transmission was examined. Reserpine partially prevented the early receptor decline but phenoxybenzamine and dimethylphenylpiperazinium did not significantly affect receptor density. The muscle was also immobilized by tenotomy, since this unique muscle is attached to the shoulder by a long, discrete tendon. Tenotomy significantly retarded the normal developmental receptor loss. It is suggested that in this muscle, muscarinic receptor density is regulated by noradrenergic nerves, possibly by a mechanism involving the transmitter, noradrenaline.     

Reserpine-induced rigidity in rats: drug effects on muscle tone from corpus striatum and nucleus accumbens

A study of the pathophysiological mechanisms of reserpine rigidity with the aid of a mechanographic method for the quantification of muscle tone. Apomorphine was used as a test substance to reduce reserpine rigidity by stimulation of dopamine receptors. Some experiments were made with additional drug treatment in an attempt to ascertain the dopaminergic specificity of the test. Apomorphine injected bilaterally to the corpus striatum has been shown to counteract the rigidity [6]. Microinjections of reserpine to corpus striatum induced rigidity with dominance in the hindleg ipsilateral to the side of injection. This rigidity was reduced by subcutaneous apomorphine. The effect of subcutaneous apomorphine on the rigidity was blocked by prior microinjection of trifluoperazine to the corpus striatum. Injections to nucleus accumbens were ineffective in all these respects. It is concluded that reserpine induces rigidity mainly by interference with the dopamine transmission in the corpus striatum.     

The influence of hypothalamically administered reserpine on the sexual behavior of the female cat

Ovariectomized cats with intracerebral implants of reserpine, a monoamine depletor, were tested for sexual behavior by introducing them to sexually vigorous males and by artificial stimulation. Approximately a third of the animals mated in response to reserpine and another third exhibited some components of sexual behavior. The behavior exhibited by these animals had none of the frenzy of normal estrous behavior. Some components of the normal pattern were missing while all others were curtailed in duration and vigor. These animals responded with normal sexual behavior to intracerebrally and systemically administered estrogen. It is suggested that the unusual sexual behavior in response to reserpine was due to the release of these behavioral patterns from a monoamine system, inhibitory to sexual behavior.     

Further studies on the interaction between bromocriptine and SKF38393 in reserpine and alpha methyl-para-tyrosine-treated mice

In a previous report, we showed that the relatively selective dopamine (DA) D-2 agonist bromocriptine (BRC), when combined with the selective D-1 agonist SKF38393, produced in DA-depleted mice a marked locomotor stimulation, despite BRC and SKF38393 being inactive by themselves (Jackson and Hashizume 1986). The present series of experiments was designed to further explore this interaction. In all experiments, mice were pretreated with reserpine and/or alpha methyl-p-tyrosine (AMPT). In mice pretreated with reserpine, AMPT or reserpine plus AMPT, BRC plus SKF38393 produced marked excitation whether the BRC was given 3 or 1 h prior to the SKF38393 challenge. However, while there was no absolute requirement that BRC be given a certain time before SKF38393, this factor was of some importance, with the onset of locomotor stimulation produced by the combination being much more rapid if the BRC was given 3 h rather than 1 h before the SKF38393. Interestingly, the degree of locomotor stimulation produced by the combination was always greatest in the animals premedicated with reserpine alone. If AMPT was also used (with or without reserpine), the stimulation produced by the combination was reduced, which may have resulted in part from a non-specific depressant effect of the AMPT. From these results, it seems as though endogenous DA is not required for BRC to work, provided that D-1 receptors are stimulated. The BRC/SKF38393 stimulation lasted for about 4 h, but could be extended for another 3 h with a second injection of SKF38393, indicating that the biological half-life of SKF38393 is the limiting factor in the duration of stimulation produced by the combination. The stimulation produced by the combination was completely blocked by the D-1 antagonist SCH23390. The data confirm the importance of D-1 receptors for the locomotor stimulant effects of BRC.     

Developmental and activity-dependent changes in K currents in satellite glial cells in mouse superior cervical ganglion

Voltage-gated K⁺ currents were recorded from freshly dissociated satellite glial cells wrapping around ganglion cells in mouse superior cervical ganglion (SCG) by whole-cell recordings of patch clamp techniques. Both inward and outward K⁺ currents during membrane hyperpolarization and depolarization were observed in these glial cells. The current-voltage relation of these K⁺ currents became almost linear in cells obtained more than 4 weeks after birth. The magnitude of the density of inward K⁺ currents, which were elicited during membrane hyperpolarization and were eliminated by external barium, progressively increased during the first month after birth. This developmental increase in the magnitude of inward K⁺ current density was not affected by decentralization of SCG done by transection of cervical sympathetic trunk (CST) 5 days after birth. In adult mice, the magnitude of the inward K⁺ current density decreased after chronic conduction blockade of CST by local application of tetrodotoxin. On the other hand, the magnitude of the inward K⁺ current density increased after daily intraperitoneal injection of reserpine and this increase was abolished by pre-treatment of decentralization of SCG. These results suggested that preganglionic innervation was not prerequisite for developmental increase in the inward K⁺ currents and preganglionic neuronal activity upregulates the inward K⁺ currents in adult mice. Neuronal regulation of glial K⁺ channel expression would assist in K+ clearance from periganglionic space to maintain neuronal activity.     

Involvement of biogenic amines in memory formation: The central nervous system indole amine involvement

Drugs administered after training and reported to alter central nervous tissue indole amine levels are shown to affect memory of a single trial passive avoidance training event of female CF-1 mice. Results indicate the normal levels of indole amines are necessary during the formative phase of memory for normal levels of memory.The author wishes to acknowledge the aid of Joan Lacktis in the initial parts of the work here reported.