The pharmacology of the behavioral and hypothermic responses of rats to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)

The hypothermic and motor behavioural responses to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) have been investigated in the rat. The dose-effect relationship showed that hypothermia appeared at a lower dose than a definite motor syndrome. The hypothermic response to 8-OH-DPAT was attenuated following depletion of 5-hydroxytryptamine (5-HT) by repeated intraperitoneal (IP) administration of parachlorophenylalanine (200 mg/kg) or by injection of 5,7-dihydroxytryptamine (5,7-DHT, 100 g) into the region of the third ventricle; the motor behavioural response produced simultaneously was not. Indeed, after 5,7-DHT, it was increased. Quipazine (1 mg/kg, IP) antagonised the hypothermic response and facilitated the motor behaviour. Clenbuterol (2.5 mg/kg, IP) increased both hypothermic and motor responses. (±)-propranolol was without effect on the simple hypermotility produced by 8-OH-DPAT, although it is known to antagonise the hypothermic and stereotyped motor responses. It is concluded that 8-OH-DPAT probably produces its hypothermic effects by actions at 5-HT receptors located presynaptically on 5-HT neurones, while the stereotyped components of the serotonin syndrome appear to be mediated by post-synaptic receptors.     

柴胡皂甙调节猫睡眠节律电活动机理的初探

目的：探讨柴胡皂甙调节猫睡眠节律活动的机理,揭示中药的的药理学作用。方法：给猫侧脑室注射色氨酸羟化酶抑制剂对氯苯丙氨酸（ＰＣＰＡ）５０ｕｌ（０．１ｍｍｏｌ／Ｌ）,以猫睡眠节律电活动为指标。用睡眠多导仪连续纪录６ｈ。结果：发现ＰＣＰＡ可造成猫睡眠剥夺状态。腹腔注射柴胡皂甙可地抗和翻转ＰＣＰＡ所致的睡眠剥夺。结论：柴胡皂甙的致眠作用。可以与脑内的５－羟色氨（５－ＨＴ）的浓度变化有关,本实验为中草药的临     

Characteristics of tetrahydrocannabinol (THC)-produced discrimination in rats

Rats were trained in a T-shaped maze to discriminate the effects produced by i.p. injections of tetrahydrocannabinol (THC) and the no-drug state (state-dependency, StD). Several doses of both ⁸-THC (range: 0.75–5.0 mg/kg) and ⁹-THC (range: 0.75–10.0 mg/kg) were used in order to compare the number of sessions required by the animals until reaching criterion performance. An additional group of rats had to discriminate pentobarbital sodium (20.0 mg/kg) from the no-drug state.Results: THC discrimination was proportional to dose i.e., animals that had to differentiate high doses of THC from no drug acquired the T-maize task faster than animals trained with the lower doses of THC. Acquisition data further suggest that ⁸-THC is somewhat less potent than the ⁹-isomer. ⁹-THC (10.0 mg/kg) produces strong StD, as defined by Overton (1971), since both this group and the barbiturate group reached the criterion within the first 10 training sessions. Time and dose testings suggest that stimulus properties of drugs vary in a quantitative way and that the calculated ED₅₀ values are mainly determined by the training dose used. It was found that the higher the training dose used the higher was the corresponding ED₅₀ value. Hashish smoke can maintain drug responding among THC-trained rats. A lowered content of brain catecholamines and/or serotonin, induced by AMPT (150 mg/kg) and PCPA (310–350 mg/kg), did not lessen ⁹-THC (2.5 mg/kg) discrimination.Portions of the results were presented at the Fourth Scandinavian Meeting on Physiology and Behavior, Oslo May 22–24, 1975.     

Alterations in the behavioral effects of LSD by motivational and neurohumoral variables.

Forty naive male albino rats were trained to press a bar on a fixed-ratio (FR 32) schedule of water reinforcement. They were then divided into two groups, one of which (N = 20) received 5 min of extra water 12 hr before each experimental session; the other group (N = 20) received no extra water. Half of the animals in each group was given three daily doses (100 mg/kg) of the trytophan hydroxylase inhibitor p-chlorophenylalanine methyl ester (PCPA) while the remaining animals were given control injections of the PCPA vehicle. Ten days following the last administration of PCPA (or vehicle) all animals were given a low dose of LSD (20 mug/kg). Bar-pressing behavior was significantly disrupted only in those animals receiving both PCPA and extra water. Central (whold brain) concentrations of serotonin (5-HT) were significantly lower in all animals which had been treated with PCPA. These results, along with those previously reported, suggest that amount of deprivation can be an important determinant of both the ability of drugs to alter behavior and the dependence of such alterations upon underlying neuronal activity.     

Parachlorophenylalanine does not affect pontine-geniculate-occipital waves in rats despite significant effects on other sleep-waking parameters

The effects of 376 mg/kg parachlorophenylalanine (PCPA) methyl ester on spontaneous and elicited pontine-geniculate-occipital (PGO) waves, locomotor activity, and sleep-staging were studied in albino rats. It was found that PCPA had no effect on the frequency per minute of spontaneously occurring PGO waves or on the relationship between elicited PGO waves and the sleep-waking cycle, which has been reported in normal rats. In contrast, significant decreases in sleep, increases in spontaneous locomotor activity, and alterations in other spontaneously emitted behaviors were observed. It was concluded that PCPA does not affect PGO waves in rats in contrast to the dramatic effects of this drug on PGO waves in cats.     

On the mechanism of fever caused by the mucopeptide of group a streptococcus

Summary Group A streptococcus mucopeptide, solubilized by ultrasonic vibrations, elicits significantly higher fever when injected into the lateral ventricle of the rabbit than if administered intravenously.Pretreatment of rabbits with reserpine, which depletes the levels of both 5-hydroxytryptamine and noradrenaline in the brain, leads to a significant inhibition of the fever response to mucopeptide. Alpha-methyl-paratyrosine is even more potent in supressing the mucopeptide hyperthermia. This potent tyrosine hydroxylase inhibitor simultaneously depletes the noradrenaline content of the brain. In contrast, the tryptophane hydroxylase inhibitor p-chlorophenylalanine, which reduces the level of hypothalamic 5-hydroxytryptamine, significantly potentiates the mucopeptide fever.     

Effects of para-chlorophenylalanine and 5-hydroxytryptophan on mouse killing behavior in killer rats.

The effects of para-chlorophenylalanine (PCPA) on mouse killing behavior were examined in natural killer rats. Forty-eight hr after injection, this serotonin synthesis inhibitor, at relatively low doses of 75 and 150 mg/kg, facilitated mouse killing, as indicated by a decrease in latency to attack the mouse. This effect was revealed in a test of satiation, in which five successive mice were presented to the rat, and also in a novel cage situation. Other than the shorter latencies to attack and kill mice, the killing response was similar in topography to the natural kill. The increase in killing after PCPA injection was associated with a reliable reduction in brain serotonin and in 5-hydroxyindoleacetic acid, and the time courses of the behavioral and biochemical changes were generally similar. In contrast to PCPA, injection of the serotonin precursor 5-hydroxytryptophan (5-HTP, 100 mg/kg) reliably lengthened attack and kill latencies in killer rats. In rats pretreated with PCPA, 5-HTP not only reversed this drug's facilitation of killing, but completely blocked killing in 67% of the rats tested. These results strengthen the hypothesis that brain serotonergic neurons are involved in the inhibition of mouse killing.     

Endogenous 5-HT inhibits firing activity of hippocampal CA1 pyramidal neurons during conditioned fear stress-induced freezing behavior through stimulating 5-HT1A receptors

This study examines the activity of hippocampal CA, pyramidal neurons during conditioned fear stress (CFS)-induced freezing behavior in unanesthetized, unrestrained rats. The firing frequency of hippocampal CA1 pyramidal neurons was significantly decreased when conditioned rats exhibited freezing behavior. Firing frequency returned to the baseline after freezing behavior disappeared. The selective 5-hydroxytryptamine (5-HT)1A antagonists, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY-100635), and N-tert-butyl-3-[4-(2-methoxyphenyl)piperazine-1-yl]-2-phenylpropamide (WAY-100135) and 5-HT depletion with parachlorophenylalanine (PCPA) completely abolished the decrease in firing frequency during CFS-induced freezing behavior. These results suggested that endogenous 5-HT inhibited the firing activity of hippocampal CA1 pyramidal neurons during CFS-induced freezing behavior mainly through stimulating 5-HT1A receptors.     

四逆散有效组分改善睡眠作用与5-羟色胺能神经系统相关性的实验研究

目的探讨四逆散有效组分改善睡眠作用与5-羟色胺（5-HT）能神经系统的相关性。方法分别观察四逆散有效组分与5-HT前体物质5-羟色氨酸（5-HTP）、5-HT合成酶抑制剂对氯苯丙氨酸（PCPA）联用,对戊巴比妥钠所致小鼠睡眠时间的影响;运用酶联免疫吸附（ELISA）法测定不同脑区5-HT的含量及其代谢产物5-羟吲哚乙酸（5-HIAA）的含量。结果阈下剂量四逆散有效组分联合5-HTP可协同延长戊巴比妥钠所致的小鼠睡眠时间（P〈0.05）;阈剂量四逆散有效组分对PCPA化小鼠睡眠时间缩短有对抗作用,PCPA亦可对抗四逆散有效组分的催眠作用;四逆散有效组分组小鼠前额叶皮质脑区5-HT的浓度明显升高（P〈0.05）,5-HIAA浓度显著降低（P〈0.05）。结论四逆散有效组分改善睡眠作用主要依赖于5-HT的存在,且延长戊巴比妥钠所致小鼠睡眠时间与5-HTP、PC-PA、5-HIAA有关。     

Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: evidence for the involvement of the monoaminergic system

Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the treatment of depression. In this study, the antidepressant-like effect of the hexanic extract from leaves of S. molle was investigated in the mouse tail suspension test (TST), a predictive model of depression. The immobility time in the TST was significantly reduced by the extract (dose range 30-600 mg/kg, p.o.), without accompanying changes in ambulation when assessed in an open-field test. The efficacy of extract was found to be comparable to that of fluoxetine (10 mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a D(2) receptor antagonist). It may be concluded that the hexanic extract of S. molle produces an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. These results provide evidence that the extract from S. molle shares with established antidepressants some pharmacological effects, at least at a preclinical level.