Erythrina mulungu Mart. ex Benth e Erythrina velutina Willd: Aspectos farmacológicos e perspectiva antroposófica de plantas brasileiras / Erythrina mulungu Mart. ex Benth and Erythrina velutina Willd: Pharmacological aspects and anthroposophic view of these Brazilian plants

As plantas brasileiras Erythrina mulungu Mart. ex Benth e Erythrina velutina Willd. têm sido utilizadas na medicina popular como sedativas e calmantes naturais para estresse, ansiedade, depressão. São plantas angiospermas, que pertencem à família das leguminosas (Fabaceae/Leguminosae) e subfamília papilionácea (Papilionaceae). Em geral são utilizados extratos das cascas do caule, frutos e folhas da E. velutina e extratos das folhas e flores da E. mulungu. Representam a principal fonte de alcaloides tetracíclicos de atividade similar ao curare, responsáveis por causar paralisia muscular. Resultados de diversos trabalhos mostraram que os alcaloides eritrartina, eritravina, 11-hidroxi-eritravina e os derivados eritrínicos são os principais responsáveis pelo efeito ansiolítico. Através de um levantamento bibliográfico sobre as plantas E. velutina e E. mulungu, no qual as propriedades terapêuticas foram avaliadas em diversos estudos pré-clínicos, observamos atividade ansiolítica com efeitos semelhante aos efeitos dos benzodiazepínicos; atividade sobre o sistema nervoso central com alteração neurotransmissora dos receptores GABA, além de ação anticonvulsivante, sedativa e amnésica; atividade antibacteriana e atividade antinociceptiva. Os aspectos antroposóficos da E. velutina e da E. mulungu apontam para as propriedades da família das leguminosas e da subfamília papilionácea. Sua principal característica é a presença do nitrogênio e o seu princípio astral. As plantas possuem apenas organização física e vital (ou etérica). A ação do anímico (ou astral) ocorre sempre de fora para dentro na planta. Com o surgimento das flores, as plantas se aproximaram do reino animal, entrando em contato com forças astrais que deveriam permanecer no exterior das plantas. Se essa astralidade penetrar na planta, isso se traduz na alteração de forma, de cor, no surgimento de substâncias, como por exemplo, os alcaloides, como tentativa da planta de impedir um processo de "animalização". Portanto, uma planta rica em alcaloides, possui propriedades pertencentes ao reino animal, e quando ingerida por seres humanos, provoca alteração da organização anímica. Assim, as plantas E. velutina e E. mulungu, ricas em alcaloides, promovem paralisia flácida no ser humano, devido à retirada da astralidade da dinâmica neuromuscular, uma vez que esta é responsável pelo tônus muscular e consciência sensorial no organismo. Essa ação deslocadora da organização anímica é responsável pelo efeito ansiolítico e sedativo em casos de distúrbios de ansiedade, estresse, tensão e insônia.(AU)

The Brazilian plants Erythrina mulungu Mart. ex Benth and Erythrina velutina Willd. have been used by the popular medicine as natural sedative and tranquilizing agent for stress, anxiety, depression and insomnia. They are angiosperm plants, which belong to the pea family (Fabaceae/Leguminosae) and the Papilionaceae subfamily. In general, the parts used are stem bark, fruits and leaves (E. velutina), and leaves and inflorescences (E. mulungu). These plants represent the main source of tetracyclic alkaloids and they have curare-like activity, causing muscular paralysis. The result of several studies demonstrated that the alkaloids erythrartin, erythravine, 11-hydroxy-erythravine and the erythrin derivatives are mainly responsible for the anxiolytic effect. After a literature review, in which the therapeutic properties of E. velutina and E. mulungu were analyzed in several preclinical studies, we observed the following: anxiolytic activity with benzodiazepine-like effects; central nervous system activity with alteration of GABA receptors, besides anticonvulsant, sedative and amnesic action; antibacterial activity and antinociceptive activity. The E. velutina and E. mulungu's anthroposophic aspects point to the properties of the pea family and the papilionaceous subfamily. The nitrogen and the astral principle are the main characteristics of these plants. Normally, plants have only physical and vital organization. However, with the flowering process, these plants get closer to the animal kingdom, getting in touch with astral forces that should remain in the external parts of the plants. If the astral forces penetrate into the plant, it will produce poison substances (alkaloids) as an attempt to avoid an "animalization" process. Therefore, an alkaloidrich plant has properties that belong to the animal sphere, and when it is used as medicine by humans, it modifies the soul organization. Thus, E. velutina and E. mulungu, which are rich in alkaloids, cause flaccid paralysis in humans due to the astrality's removal from neuromuscular dynamics, once it is responsible for muscle tone and sensory awareness in the body. This dislocated action of the soul organization is responsible for the anxiolytic and sedative effects in cases of anxiety, stress, tension and insomnia.(AU)

Efecto sedante del extracto alcóholico de hojas y flores de Melissa officinalis "Toronjil" más Matricaria chamomilla "Manzanilla" sobre la ansiedad inducida en ratones albinos / Sedative effect of the alcoholic extract of leaves and flowers of Melissa officinalis "Toronjil" plus Matricaria chamomilla "Chamomile" on anxiety induced in albino mice

Introducción: Ansiedad enfermedad del milenio, el cual requiere tratamiento para evitar trastorno mayores. Objetivo: Determinar efecto sedante de Melissa officinalis "Toronjil" más Matricaria chamomilla "Manzanilla" sobre ansiedad inducida en ratones albinos. Diseño: Experimental. Lugar: Facultad de Medicina y Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos. Material Biológico: ratones, ratas albinos. Intervenciones: Treintaises ratones fueron inducidos a hiperactividad y/o cambios conductuales por NMDA, considerándose grupos 1) SSF 10 mL/kg; 2) NMDA 75 mg/kg; 3, 4, 5) NMDA + Extracto 1, 2, 4 g/Kg correspondientemente, y 6) NMDA + DAP-7 antagónico del NMDA 0.33 nmol/kg; observándose hiperactividad, cambios conductuales, periodo latencia en minutos y porcentaje de protección. Se comparó el efecto sedante con diazepam en 30 ratones: 1) SSF 10 mL/kg; 2) diazepam 50 mg/kg; 3, 4, y 5) Extracto 1, 2, 4 g/kg respectivamente, midiéndose tiempo de dormir (minutos). Se realizó el estudio de estudio de toxicidad crónica a 60 días en 20 ratas divididos en 4 grupos: 1, 2 blanco control 3, 4, (extracto alcohólico) a dosis de 4 g/Kg. por vía oral, se evaluó los niveles tóxicos determinando a nivel, Bioquímicos: urea, colesterol, transaminasas, lipoproteína HDL e histología. Resultados: Los compuestos fenólicos y terpenoídes estuvieron en mayor cantidad en el extracto alcohólico; el 100% (p<0.05) de ratones mostró efecto sedante; los hallazgos hematológicos, bioquímicos se encontraron dentro de los límites aceptados; e histopatológicamente no hubo evidencia de cambios morfológicos. Conclusiones: El extracto alcohólico de hojas y flores de Melissa officinalis "Toronjil" más Matricaria chamomilla "Manzanilla" es sedante en ratones, y sin toxicidad en ratas.

Comparación del efecto del extracto de Valeriana prionophylla Standl versus placebo sobre la ansiedad de 30 pacientes en tratamiento de quimioterapia por cáncer de mama, durante 4 semanas, en hospital de cancerología Incan Guatemala / Comparison of the effect of the extract of Valeriana prionophylla Standl versus placebo on the anxiety of 30 patients undergoing chemotherapy treatment for breast cancer, for 4 weeks, at the hospital of cancerology Incan Guatemala

Las pacientes con cáncer de mama desde su diagnóstico inicial experimentan diversos de grados de ansiedad, lo cual puede corroborarse al hacer un sondeo en las clínicas de atención de pacientes.(4) Partiendo de una evaluación inicial, mediante el Test de Hamilton para ansiedad, se pudo evidenciar la existencia de ansiedad en el 100% de pacientes con cáncer de mama que acuden a su tratamiento de quimioterapia. Fueron evaluadas inicialmente 40 pacientes a quienes se les proporciono, como tratamiento extracto de Valeriana prionophylla a 20 pacientes, así como extracto de maíz, como placebo a las otras 20 escogidas al azar, se conservo la información del contenido de los frascos para el final del estudio, con el objeto de hacerlo doble ciego controlado (ni el autor, ni el paciente conocieron si no hasta el final el tipo de tratamiento tomado). Se administro un extracto de Valeriana prionophylla guatemalteca, preparado por Laboratorio Farmaya en dilusion 1:5, a dosis de 30 gotas por la mañana y 30 gotas por la tarde, equivalentes a 600mg diarios. Finalizaron el estudio 30 pacientes, 15 de tratamiento y 15 placebo, quienes fueron reevaluados vía telefónica nuevamente mediante el Test de Hamilton. Se elaboró una base de datos, a la cual se le practico la Prueba exacta de Fisher asi como el Test de Chi Cuadrado, como análisis estadístico. Las conclusiones del estudio fueron las siguientes: 1. Todas las pacientes bajo tratamiento de quimioterapia por cáncer de mama manifiestan algún grado de ansiedad. 2. El extracto de Valeriana, redujo el nivel de ansiedad a valores normales en todas las pacientes bajo tratamiento, evidenciando un efecto positivo y beneficioso en la calidad de vida de este tipo de pacientes, confirmando lo que indica la literatura.(9,10.11,12) 3. El extracto de Valeriana supero el efecto placebo del extracto de maíz en las pacientes bajo tratamiento.

Psicoterapia en ataques de pánico / Psychotherapy in panic attacks

Los ataques de pánico conforman una manifestación particular de los transtornos por ansiedad y su aproximación psicoterapéutica requiere además de la intervención del transtorno de ansiedad, otras intervenciones específicas. Considerando que los ataques de pánico han sido inducidos mediante la presentación de imágenes, las evidencias del rol del "significado" y "atribuciones" como desencadenantes del ataque; se plantea la necesidad de la expocición imaginaria como instrumento psicoterapéutico. En este trabajo se describe el modelo cognitivo de la ansiedad y se propone un modelo terapéutico cognitivo estructurado con fundamento experimental para el tratamiento de los ataques de pánico. Los ataques de pánico conforman una manifestación particular de los transtornos por ansiedad y aun cuando constituyen una entidad clínica con características y criterios diagnósticos particulares la aproximación psicoterapéutica debe involucrar la intervención del transtorno de ansiedad así como intervenciones específicas para tratar los ataques de pánico

Behavior of mother rats in conflict tests sensitive to antianxiety agents.

Previous studies of freezing and open-field activity have demonstrated that lactating rats are less fearful or less anxious than nonpregnant ones. The purpose of this investigation was to observe the behavior of mother rats in conflict tests, which are frequently used in studies on the neurobiology of anxiety. In the punished drinking test, in which licking from a water spout is punished by electric shocks, mothers (observed on Day 1 postpartum following 24 hr of water deprivation) were found to drink more than virgins. Mothers (Day 1 postpartum) also consumed more food than controls in an unfamiliar open field. In contrast, no difference between mothers (Day 5 postpartum) and virgins was present in the exploration of an electrified shock probe. The largest maternal anticonflict effects in the drinking and feeding tests were recorded when the females were tested with their pups. Increased punished drinking was also observed in virgin rats treated with the anxiolytic benzodiazepine midazolam. Water-deprived virgins and mothers did not differ in the shock titration test, a result suggesting that diminished pain reactivity was unlikely to account for the increased punished drinking in mothers. Moreover, females in late pregnancy, which are hypoalgesic (Gintzler, 1980), did not lick more than virgins in the punished drinking test. Following 24 hr of water deprivation, unpunished drinking was higher in lactating females than in virgins, so the increased acceptance of punishment by mothers might have been due to their being more thirsty than virgins.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha 2-adrenoceptor antagonists potentiate the anticonflict and the rotarod impairing effects of benzodiazepines.

Putative interactions between the specific alpha 2-adrenoceptor antagonist idazoxan and benzodiazepines (BDZs) were examined in two different rat conflict models; Vogel's drinking conflict test (VT) and Montgomery's conflict test (MT) (the elevated +-maze). In the MT, idazoxan (0.031 mg/kg) produced anxiogenic-like effects, which were counteracted both by the triazolo-BDZ alprazolam (APZ; 0.2 mg/kg) and the conventional BDZ diazepam (DIZ; 0.2 mg/kg). In fact, the anxiolytic-like effects of APZ were significantly potentiated when co-administering idazoxan. A tendency to such a phenomenon was seen also in rats treated with DIZ and idazoxan. In the VT, the anxiolytic-like effects both of APZ (1.0 mg/kg) and DIZ (4.0 mg/kg) were significantly enhanced when co-administering idazoxan (1.0 mg/kg) in a dose not affecting the behavior per se. Similar potentiating phenomena by behaviorally inert doses of alpha 2-adrenoceptor antagonists (idazoxan 1.0 mg/kg; yohimbine 2.0 mg/kg) were seen with regard to the ataxic/sedative effects of the BDZs (APZ 0.25 mg/kg; DIZ 1.5 mg/kg). The present results provide further support for the notion that the anxiolytic-like effects of BDZs are not related to attenuation of Locus Coeruleus activity. In addition, it is suggested that the potentiation caused by the alpha 2-adrenoceptor antagonist is mediated via a noradrenaline induced increase in signal-to-noise ratio in target neurons of the brain noradrenergic system.

Does the PCPA induced anticonflict effect involve activation of the GABAA/benzodiazepine chloride ionophore receptor complex?

The effects of the benzodiazepine (BDZ) receptor antagonist flumazenil (Ro 15-1788) and the GABAA receptor antagonist bicuculline on the anticonflict effect observed after depletion of brain serotonin (5-HT), were examined in a modified Vogel's punished drinking conflict model. Pretreatment with para-chlorophenylalanine (PCPA; 300 mg/kg/day for three days, last injection - 24 h) markedly decreased brain 5-HT levels and produced clearcut anticonflict effects. The anticonflict effect, but not the biochemical effect, of PCPA pretreatment was completely counteracted by both flumazenil (10 mg/kg, - 30 min) and bicuculline (2.0 mg/kg, - 10 min), in doses not altering the behavior per se. The findings suggest a behavioral interaction between 5-HT systems and the GABAA/BDZ chloride ionophore receptor complex, possibly involving a direct neuronal interaction, neuromodulation or hormonal alterations.

Effects of cocaine on conflict behavior in the rat.

The present studies examined the effects of acute cocaine administration, chronic cocaine administration and cocaine withdrawal on behavior in the Conditioned Suppression of Drinking (CSD) conflict paradigm, an animal model for the study of anxiety. In daily 10-minute sessions, water deprived rats were trained to drink from a tube that was occasionally electrified (0.25 mA), electrification being signalled by a tone. Within 3-4 weeks, control (i.e., non-drug) CSD behavior stabilized (30-50 shocks and 10-12 ml/session) and drug studies were initiated. Acute administration of cocaine (30-min pretreatment) produced a selective pro-conflict effect only at a dose of 10 mg/kg cocaine, with lower doses (2.5, 5 mg/kg) exerting no effect on CSD behavior and a higher dose (20 mg/kg) depressing both punished and unpunished responding. In a second experiment, cocaine (10 mg/kg, IP, 2/day) or saline was administered to separate groups of subjects for 7 weeks. In this chronic treatment study, CSD testing was conducted 12 hours after each evening cocaine administration. Although it had no effect on CSD behavior during the first week of treatment, this chronic cocaine administration produced a significant and selective pro-conflict effect which was stable during the period from Weeks 2-7. In a final experiment, a high dose of cocaine (20 mg/kg, 3/day) or saline was given to separate groups of subjects for 2 weeks and the behavioral effects of these treatments and their subsequent termination were examined. In this study, CSD testing was conducted 8 hours after each evening cocaine treatment. During the first week of high dose cocaine treatment, a decrease in punished responding was observed; this parameter returned to baseline levels by Week 2. Discontinuation of this high dose chronic cocaine treatment resulted in a selective decrease in punished responding. This pro-conflict effect was greatest at 3 days, and lasted for 6 days after the last cocaine dose. These data are consistent with clinical findings demonstrating the anxiogenic effects of both acute and chronic cocaine treatment as well as cocaine withdrawal and suggest that conflict paradigms such as the CSD may be useful for the study of cocaine-induced anxiety states.

The effects of FG 7142 upon local cerebral glucose utilization suggest overlap between limbic structures important in anxiety and convulsions.

The effects of the beta-carboline benzodiazepine receptor ligand FG 7142 upon local cerebral glucose utilization have been examined in conscious rats using the quantitative [14C]2-deoxyglucose autoradiographic technique. FG 7142 (1-10 mg/kg i.v.) produced behavioural changes consistent with an anxiogenic action. At the largest dose of FG 7142 (10 mg/kg) 30% of the animals experienced overt convulsions. In the data analysis animals were divided according to the behavioural response elicited by the drug. In animals not expressing convulsions, FG 7142 (1-10 mg/kg) effected increases in glucose utilization in 33 of the 65 regions examined. The majority of changes were confined to limbic structures with pronounced effects occurring in the mammillary body, anterior thalamic nuclei, septal nuclei and the oriens and molecular layers of the hippocampus. Glucose use in other structures associated with auditory and visual processing, such as the medial and lateral geniculate body, and associated cortical areas, was also significantly increased. However, brain regions involved in motor control were minimally affected. The patterns of local cerebral glucose use in animals expressing FG 7142-induced convulsions were contrasted with those from an equivalent non-seizure group. Some limbic structures which were significantly affected by FG 7142 (non-seizure group) displayed a further increase in glucose utilization during convulsions. These included the mammillary body and septum. Many other limbic structures (anterior thalamic nuclei, CA fields of the hippocampus and basolateral amygdala) did not display this further rise in glucose utilization. In the cortical amygdala, lateral preoptic area of the hypothalamus, nucleus accumbens and lateral elevations in glucose utilization were restricted to those animals experiencing overt convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Propranolol antagonizes the enhanced conditioned fear produced by corticotropin releasing factor.

A series of experiments examined the effects of systemic administration of the beta adrenergic antagonist propranolol on the enhanced conditioned fear and the locomotor hyperactivity induced by central administration of corticotropin releasing factor (CRF). In Experiment 1, CRF (0.5 microgram) was shown to reduce responding in both the conditioned stimulus (cs) and the pre-cs components of an on-the-base-line conditioned suppression schedule. The effects of CRF on cs, but not pre-cs responding were antagonized by propranolol, at doses (2.5, 5.0 and 10.0 mg/kg) that did not affect responding themselves. This reversal of the anxiogenic effects of CRF by propranolol was specific to l- and not d-propranolol, showing that it did not result from nonspecific membrane stabilization. Propranolol also failed to reverse the reduced responding induced by the benzodiazepine inverse agonist FG 7142 in this schedule. In Experiment 2, propranolol was shown to potentiate the locomotor hyperactivity induced by CRF in a familiar photocell cage. These results suggest that activation of beta adrenoceptors may be an important mechanism in the behavioral inhibition induced by CRF, and that the neurochemical mechanisms that underlie the "anxiogenic" and the "activating" behavioral effects of CRF are neuropharmacologically distinct.

A double-blind comparison between nitrazepam, lorazepam, lormetazepam and placebo as preoperative night sedatives.

Benzodiazepines are used as hypnotics to reduce anxiety and give a good night's sleep on the night prior to surgery. In a double-blind procedure, patients were given either lorazepam (2 mg or 4 mg), lormetazepam (1 mg or 2 mg), nitrazepam 10 mg or placebo. Measures were taken of sleep, anxiety, memory and after-effects. There was no evidence that the drugs reduced anxiety, nor evidence of amnesia. Quality and length of sleep was shown to be better for nitrazepam (P less than 0.05), lorazepam 2 mg (P less than 0.05) and lorazepam 4 mg (P less than 0.01), compared with placebo. However, significantly higher ratings of clumsiness and confusion as after-effects were found with nitrazepam (P less than 0.05), and clumsiness (P less than 0.005), slurred speech and blurred vision (P less than 0.01), sleepiness, nausea, weakness and confusion (P less than 0.05) with lorazepam 4 mg. It was concluded that lorazepam 2 mg produced the greatest net benefit.

Chlordiazepoxide and the drinking of water by rats: effects of shock and other suppressive measures.

The effects of chlordiazepoxide (5 and 10 mg/kg) on fluid consumption in water deprived rats were assessed. Drinking was inhibited to approximately equal extents by a water preload, by d-amphetamine (1.5 mg/kg), by neophobia and by shock at mild (0.3 mA) or moderate (0.5 mA) intensities, the latter condition having an enhanced level of deprivation also. At both doses chlordiazepoxide significantly enhanced drinking in the neophobia, mild shock and, especially, the moderate shock condition but failed to increase drinking suppressed by preload or d-amphetamine. It is concluded that the increases in drinking suppressed by neophobia or shock which chlordiazepoxide induces may be due to anxiolytic actions of the drug or to enhanced palatability since they cannot be explained in terms of nonspecific enhancement of fluid consumption.

Interactions of three benzodiazepine receptor inverse agonists with ethanol in a plus-maze test of anxiety.

The effects of RO 15-4513, RO 15-3505 and FG 7142 on the anxiolytic properties of ethanol in mice were investigated using the plus-maze test of anxiety. Before being tested on the plus-maze, the mice were tested in a holeboard apparatus. All three inverse agonists attenuated the reduction in exploration caused by ethanol in the holeboard test. In the plus-maze, only RO 15-4513 and FG 7142, which possess anxiogenic properties when administered alone, attenuated ethanol's anxiolytic effect. RO 15-3505, which alone had no effect on anxiety, failed to significantly reduce ethanol's anxiolytic effect. Neither RO 15-4513 nor FG 7142 reduced the increase in the total number of arm entries caused by ethanol. These data indicate that the interaction between ethanol and benzodiazepine receptor ligands depends both on the intrinsic properties of the ligands and the behavior under investigation.

Actions of buspirone in a putative model of anxiety in the mouse.

In a two-compartment box divided into a dark area and a brightly illuminated white area, mice taken from a dark environment showed aversion to the light and exhibited preference for exploratory rearings and line crossings in the black area. The peripheral administration of buspirone, and its injection into the dorsal raphe nucleus, lead to an increased time spent in the white area associated with enhanced exploratory behaviour with a decreased incidence of rearings and line crossings in the black section. In contrast, the injection of 5-hydroxytryptamine and 2-methyl-5-hydroxytryptamine into the dorsal raphe nucleus increased exploratory behaviour in the black section with decreased activity in the white area: the effects of 2-methyl-5-hydroxytryptamine were antagonized by buspirone administered peripherally. Ritanserin, methysergide, metergoline and cyproheptadine failed, in non-sedative doses, to influence exploratory behaviour in the two-compartment system and ritanserin and methysergide also failed to antagonize the effects caused by 2-methyl-5-hydroxytryptamine. It is concluded that in the mouse model the ability of buspirone to reduce the aversive response to a brightly illuminated area may reflect an anxiolytic action, that the dorsal raphe nucleus may be an important locus of action, and that the effects of buspirone may reflect an interaction at 5-hydroxytryptamine receptors.

An efficacy study of isocarboxazid and placebo in depression, and its relationship to depressive nosology.

Isocarboxazid and placebo were evaluated in 130 anxious depressives. Drug was superior to placebo on depression, anxiety, interpersonal sensitivity, and global measures, and on symptoms of hostility, anxiety, obsessiveness, and psychological-cognitive components of depression. There were no significant differences between treatment effects on psychomotor and typical vegetative symptoms. Isocarboxazid was more effective than placebo in major, but not in minor, depression. It was significantly more effective in depression classified as endogenous depression or melancholia by various diagnostic criteria. Drug was more effective than placebo in atypical depression with vegetative reversal and in Brief Psychiatric Rating Scale (BPRS)-derived profiles of anxious and hostile depression; there were no drug-placebo differences in atypical depression without vegetative reversal, or in BPRS retarded and agitated/excited depression. Interpersonal sensitivity emerged as an important drug-responsive dimension.

l-fenfluramine in tests of dominance and anxiety in the rat.

l-Fenfluramine (1.25 and 2.5 mg/kg) significantly reduced the success of dominant rats competing with untreated middle rank rats for chocolate. In resident rats, l-fenfluramine (2.5 mg/kg) significantly increased the number of submissions, and the time spent submitting, to untreated rats intruding into their home-cage territory; it also significantly reduced the number of kicks directed at, and the time spent kicking, the intruder; and the incidence of, and time spent in, aggressively grooming the intruder. When the intruder rats were treated with l-fenfluramine the only significantly change was a decrease in the number of wrestling bouts and the time spent wrestling. Since l-fenfluramine did not change other behaviours in this test (e.g. sniffing the opponent) the decrease in dominance behaviours was probably not secondary to nonspecific sedation. In the social interaction test of anxiety, l-fenfluramine (2.5 and 5 mg/kg) significantly reduced the time spent in active social interaction, and decreased motor activity. Analyses of covariance indicated that these were two independent effects. In the elevated plus-maze, l-fenfluramine (1.25-5 mg/kg) significantly decreased the percent number of entries made onto open arms, and (2.5 and 5 mg/kg) significantly decreased the percent of times spent on the open arms. The total number of arm entries was reduced by all doses (0.625-5 mg/kg). Analysis of covariance indicated that the decrease in percent of time spent on the open arms was secondary to the drop in overall activity. Thus there was no evidence of anxiolytic action in either of these tests, the changes indicating, if anything, anxiogenic effects.(ABSTRACT TRUNCATED AT 250 WORDS)