Acupuncture attenuates comorbid anxiety- and depressive-like behaviors of atopic dermatitis through modulating neuroadaptation in the brain reward circuit in mice

Atopic dermatitis (AD) is highly comorbid with negative emotions such as anxiety and depression. Although acupuncture has demonstrated efficacy in AD, its influence on comorbid anxiety and depression remains unclear. We sought to explore the impact and mechanisms of action of acupuncture on comorbid anxiety and depression of AD. AD-like skin lesions were induced by the topical application of MC903 to the mouse cheek. Acupuncture was performed at Gok-Ji (LI11) acupoints. AD-like phenotypes were quantified by lesion scores, scratching behavior, and histopathological changes. The effects of acupuncture on comorbid anxiety and depression-like behaviors were assessed using the elevated plus-maze (EPM), open-field tests (OFT), and tail-suspension test (TST). In addition, biochemical changes in the brain reward regions were investigated by immunoblotting for the expression of tyrosine hydroxylase (TH), dopamine D1 receptor (D1R), phospho-dopamine and cAMP-regulated phosphoprotein-32 kDa (pDARPP-32), phospho-cAMP response element binding protein (pCREB), ΔFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens, dorsolateral striatum, and ventral tegmental area. Acupuncture effectively improved the chronic itching and robust AD-like skin lesions with epidermal thickening. Additionally, it considerably reduced comorbid anxiety- and depression-like symptoms, as indicated by more time spent in the open arms of the EPM and in the center of the open field and less time spent immobile in the TST. Higher pCREB, ΔFosB, BDNF, and pDARPP-32 levels, and reduced TH and D1R protein expression in the brain reward regions of AD mice were reversed by acupuncture treatment. The beneficial effects of acupuncture on clinical symptoms (scratching behavior) and comorbid psychological distress in AD strongly correlated with dorsal striatal ΔFosB levels. Collectively, these data indicate that acupuncture had a significant, positive impact on comorbid anxiety- and depression-like behaviors by modulating neuroadaptation in the brain reward circuit in mice with AD, providing a novel perspective for the non-pharmacological management of psychiatric comorbidities of AD.

Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice

The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old) received ayahuasca or water (1.5 mL/kg, orally) twice a week for 12 months and were tested in the Morris water maze (MWM), open field and elevated plus maze (EPM) tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition) of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice.

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

Envolvimento de receptores 5-HT2C do hipocampo ventral em comportamentos de defesa de ratos no labirinto em cruz elevado / Involvement of ventral hippocampus 5-HT2C receptors on defensive behaviors of rats in the elevated plus-maze

A ativação farmacológica dos receptores 5-HT2C induz comportamentos de defesa em modelos animais. O estudo busca investigar se o bloqueio seletivo de receptores 5-HT2C no hipocampo ventral (HV) previne comportamentos defensivos induzidos por um agonista de receptor 5-HT2C administrado perifericamente em ratos expostos ao labirinto em cruz elevado (LCE). Quinze minutos após injeções intraperitoniais (IP, 1ml/kg) do agonista 5-HT2C WAY-161503, ratos foram microinjetados bilateralmente no HV com o antagonista seletivo de receptores 5-HT2C SB-242084 (0, 0,1, 0,5 ou 1.5μg). Dez minutos após, cada animal foi exposto ao LCE para o registro de categorias de ansiedade. Injeções sistêmicas do WAY-161503 reduziram seletivamente as explorações nos braços abertos e aumentaram padrões de avaliação de risco. Esse efeito foi atenuado de maneira dose-dependente pela microinjeção de SB-242084 no HV, confirmando a ação ansiogênica de agonistas 5-HT2C e sugerindo que esse perfil comportamental seja mediado, pelo menos em parte, por receptores 5-HT2C do HV.

Pharmacological 5-HT2C receptor activation induces defensive behaviors in several animal models of anxiety. The present study investigated whether the selective blockade of 5-HT2C receptors in the ventral hippocampus (VH) prevents defensive behaviors induced by a 5-HT2C agonist administered systemically in rats exposed to the elevated plus-maze (EPM). Fifteen minutes after intraperitonial (IP, 1ml/kg) injections of the selective 5-HT2C receptor agonist WAY-161503 (3 mg/kg), rats were bilaterally microinjected with the selective 5-HT2C antagonist SB-242084 (0, 0.1, 0.5 or 1.5μg) into the VH. Ten minutes after, each animal was exposed to the EPM for measuring classical and ethological anxiety measures. IP WAY-161503 injections selectively decreased open-arm exploration while increasing risk-assessment. This anxiogenic-like action was dose-dependently attenuated by intra-VH SB-242084 microinjections. These results not only further confirm the anxiogenic-like action of 5-HT2C agonists, but also suggest that this behavioral profile might be mediated at least in part by VH 5-HT2C receptors.

Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice

Anxiolytic and anxiogenic-like behavioral outcomes have been reported for methylenedioxymethamphetamine (MDMA or ecstasy) in rodents. In the present experiment, we attempted to identify behavioral, hormonal and neurochemical outcomes of MDMA treatment to clarify its effects on anxiety-related responses in 2-month-old Balb/c male mice (25-35 g; N = 7-10 mice/group). The behavioral tests used were open field, elevated plus maze, hole board, and defensive behavior against predator odor. Moreover, we also determined striatal dopamine and dopamine turnover, and serum corticosterone levels. MDMA was injected ip at 0.2, 1.0, 5.0, 8.0, 10, or 20 mg/kg. MDMA at 10 mg/kg induced the following significant (P < 0.05) effects: a) a dose-dependent increase in the distance traveled and in the time spent moving in the open field; b) decreased exploratory activity in the hole board as measured by number of head dips and time spent in head dipping; c) increased number of open arm entries and increased time spent in open arm exploration in the elevated plus maze; d) increased time spent away from an aversive stimulus and decreased number of risk assessments in an aversive odor chamber; e) increased serum corticosterone levels, and f) increased striatal dopamine level and turnover. Taken together, these data suggest an anxiogenic-like effect of acute MDMA treatment, despite the fact that behavioral anxiety expression was impaired in some of the behavioral tests used as a consequence of the motor stimulating effects of MDMA.

Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice

OBJECTIVE: Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. METHOD: Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16) had access to sugarcane spirit + distilled water, the mice in Group B (n = 15) had access to ethanol + distilled water, and the mice in Group C (control, n = 14) had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2 percent for the first week, 5 percent for the second week and 10 percent for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. RESULTS: In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 + 8 vs. 7 + 2 s, n = 9) or sugarcane spirit (36 + 9 vs. 7 + 2 s, n = 9) compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 + 1 for the control group, 27 + 2 for the ethanol group, and 31 + 3 for the sugarcane-spirit group; n = 9 for each group). In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 + 0.17 for the control group and 2.67 + 0.17 for the sugarcane spirit group; n = 8 for each group). CONCLUSION: The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

L-histidine provokes a state-dependent memory retrieval deficit in mice re-exposed to the elevated plus-maze

The effects of L-histidine (LH) on anxiety and memory retrieval were investigated in adult male Swiss Albino mice (weight 30-35 g) using the elevated plus-maze. The test was performed on two consecutive days: trial 1 (T1) and trial 2 (T2). In T1, mice received an intraperitoneal injection of saline (SAL) or LH before the test and were then injected again and retested 24 h later. LH had no effect on anxiety at the dose of 200 mg/kg since there was no difference between the SAL-SAL and LH-LH groups at T1 regarding open-arm entries (OAE) and open-arm time (OAT) (mean ± SEM; OAE: 4.0 ± 0.71, 4.80 ± 1.05; OAT: 40.55 ± 9.90, 51.55 ± 12.10, respectively; P > 0.05, Kruskal-Wallis test), or at the dose of 500 mg/kg (OAE: 5.27 ± 0.73, 4.87 ± 0.66; OAT: 63.93 ± 11.72, 63.58 ± 10.22; P > 0.05, Fisher LSD test). At T2, LH-LH animals did not reduce open-arm activity (OAE and OAT) at the dose of 200 mg/kg (T1: 4.87 ± 0.66, T2: 5.47 ± 1.05; T1: 63.58 ± 10.22; T2: 49.01 ± 8.43 for OAE and OAT, respectively; P > 0.05, Wilcoxon test) or at the dose of 500 mg/kg (T1: 4.80 ± 1.60, T2: 4.70 ± 1.04; T1: 51.55 ± 12.10, T2: 43.88 ± 10.64 for OAE and OAT, respectively; P > 0.05, Fisher LSD test), showing an inability to evoke memory 24 h later. These data suggest that LH does not act on anxiety but does induce a state-dependent memory retrieval deficit in mice.

Alterações neuro-comportamentais em ratos machos adultos em modelos de programação pela hiperleptinemia na lactação / Neuro-behavioral alterations in adult male rats in programming models for hyperleptinemia in lactation

Existe uma grande associação entre alterações em parâmetros nutricionais, hormonais ou ambientais durante estágios iniciais da vida, particularmente durante os períodos gestacional e de lactação, e o surgimento de doenças crônicas na vida adulta tais como obesidade, diabetes, doenças cardiovasculares, ansiedade e depressão. Neste trabalho, foram avaliados os efeitos cognitivo-comportamentais, em ratos Wistar adultos, da administração de leptina (8ug/100g, dia, sc) durante os primeiros 10 dias de lactação: 1) diretamente nos filhotes; 2) nas progenitoras. A memória e o aprendizado, os níveis de comportamento associados à ansiedade e à busca pela novidade foram avaliados em animais adultos através, respectivamente, dos seguintes testes comportamentais: labirinto aquático radial de 8 braços, labirinto em cruz elevado e campo vazado. No primeiro modelo (injeção nos filhotes), foram observados altos níveis de ansiedade e de busca por novos estímulos, enquanto que a memória e aprendizagem e atividade locomotora não foram afetados. No segundo modelo (injeção nas progenitoras), foram detectados redução dos níveis de ansiedade e melhora no desempenho associado à memória e ao aprendizado. Porém, não houve diferença nos níveis de busca por novos estímulos e no nível de atividade locomotora. Também são observadas diferenças em parâmetros somáticos, endócrinos e metabólicos entre modelos. O primeiro modelo resulta em hiperfagia, maior peso corporal por aumento de massa magra, hiperleptinemia, hipertireoidismo, hipertrigliceridemia, hiperinsulinemia e hipoadiponectinemia, hipertensão, aumento de catecolamina e de corticosterona, além de resistência hipotalâmica à leptina. O segundo modelo induz hiperfagia e maior peso corporal por acúmulo de gordura, hiperleptinemia, hiperglicemia, eutireoidismo, normoinsulinemia e resistência central à leptina. As seguintes possibilidades podem explicar as diferenças cognitivos-comportamentais observadas entre os modelos estudados ...

A considerable association exists between variations in the gestational and lactation periods, and the appearance of chronic diseases in adult life, such as obesity, diabetes, cardiovascular diseases, anxiety and depression. In the present study, the cognitive and behavioral effects of leptin injection (8ug/100g/day, sc) during the first 10 days of lactation were evaluated in adult male Wistar rats. In the first part of the study, leptin was injected directly in the offspring. In the second part of the study, leptin was injected in the lactation dams. Memory and learning, levels of anxiety-like behavior and levels of novelty-seeking behavior were evaluated by testing animals in, respectively, the radial-arm water maze, the elevated plus maze and the hole board arena. In the first model (offspring injection), high levels of anxiety and of novelty-seeking behavior were observed. Memory/learning and locomotor activity were unaffected. In the second model (dam injection), reduced levels of anxiety and better memory/learning performance were observed. Conversely, novelty-seeking and locomotor behavior were unaffected. Differences between models regarding somatic, endocrine and metabolic parameters are also observed. The first model presents hyperphagia, higher lean body mass, hyperleptinemia, hyperthyroidism, hipertrigliceridemia, hiperinsulinemia and hypoadiponectinemia, hypertension, increased levels of catecholamines and corticosterone, and hypothalamic leptin resistance. The second model induces hyperphagia, higher body mass, thou by accumulation of fat, hyperleptinemia, hyperglycemia, euthyroidism, normoinsulinemia and central mechanism of leptin resistance. The following possibilities may explain the cognitive-behavioral differences observed between models in the present study: 1) differences in somatic, endocrine and metabolic parameters; 2) modifications of the relationship between dams and their offspring, since leptin injection in the dams may reduce ...

Involvement of adenosinergic receptors in anxiety related behaviours.

In the present study, the effect of adenosine (A1 and A2 receptor agonist), caffeine (A2A receptor antagonist), theophylline (A2A receptor antagonist) and their combination was studied in anxiety related behaviours using elevated zero maze and elevated plus maze paradigms and compared their various behavioural profiles. Adenosine (10, 25, 50,100 mg/kg) significantly showed anxiolytic effect at all the doses, whereas caffeine (8, 15, 30, 60 mg/kg) and theophylline (30, 60 mg/kg) showed psychostimulatory action at lower doses and anxiogenic effect at higher doses. Pretreatment with caffeine (8, 15, 30 mg/kg) and theophylline (30 mg/kg) reversed the anxiolytic effect of adenosine. The study suggested the involvement of adenosinergic receptor system in anxiety related behaviours.

Ansiedade experimental humana / Human experimental anxiety

CONTEXTO: A ansiedade experimental no ser humano constitui-se em ponte entre os modelos animais e os ensaios clínicos. OBJETIVO: Este artigo focaliza métodos químicos e psicológicos utilizados para provocar ansiedade experimental em seres humanos. MÉTODOS: Realizou-se revisão seletiva da literatura. RESULTADOS: Os desafios farmacológicos têm sido usados principalmente para induzir ataques de pânico em pacientes com transtorno de pânico, os quais são mais sensíveis a eles que indivíduos normais ou pacientes portadores de outros transtornos psiquiátricos. Uma das mais importantes contribuições deste método é a de ter mostrado que os agentes panicogênicos mais seletivos, como o lactato ou a inalação de CO2, não ativam o eixo hormonal do estresse. Entre os métodos psicológicos, destacam-se o condicionamento de respostas elétricas da condutância da pele, cujo perfil farmacológico se aproxima daquele do transtorno de ansiedade generalizada, e o teste da simulação do falar em público, cuja farmacologia é semelhante à do transtorno de pânico. CONCLUSÕES: Tais resultados salientam a diferença entre a neurobiologia da ansiedade e a do pânico.

BACKGROUND: Human experimental anxiety methods bridge the gap between animal models and clinical assays. OBJECTIVE: This article is focused on chemical and psychological procedures used to generate experimental anxiety in human beings. METHODS: A selective review of the literature has been carried out. RESULTS: Pharmacological challenges have been mainly used to induce panic attacks in panic disorder patients, who are more susceptible than normal individuals or patients with other psychiatric disorders. One of the most important contributions of this method is to have shown that the most selective panicogenic agents, such as lactate or CO2 inhalation, do not activate the hormonal stress axis. Among the psychological methods stand the conditioning of the electrical skin conductance response, which has a pharmacological profile similar to that of generalized anxiety disorder, and the simulated public speaking test, which is pharmacologically similar to panic disorder. CONCLUSIONS: These results highlight the difference between the neurobiology of anxiety and that of panic.

Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin

The objective of the present study was to determine if the acute behavioral effects of cocaine acutely administered intraperitoneally (ip) at doses of 5, 10 and 20 mg/kg on white male CF1 mice, 90 days of age, would be influenced by leptin acutely administered ip (at doses of 5, 10 and 20 æg/kg) or by endogenous leptin production enhanced by a high-fat diet. The acute behavioral effects of cocaine were evaluated in open-field, elevated plus-maze and forced swimming tests. Results were compared between a group of 80 mice consuming a balanced diet and a high-fat diet, and a group of 80 mice fed a commercially available rodent chow formula (Ralston Purina) but receiving recombinant leptin (rLeptin) or saline ip. Both the high-fat-fed and rLeptin-treated mice showed decreased locomotion in the open-field test, spent more time in the open arms of the elevated plus-maze and showed less immobility time in the forced swimming test (F(1,68) = 7.834, P = 0.007). There was an interaction between diets and cocaine/saline treatments in locomotion (F(3,34) = 3.751, P = 0.020) and exploration (F(3,34) = 3.581, P = 0.024). These results suggest that anxiolytic effects and increased general activity were induced by leptin in cocaine-treated mice and that low leptin levels are associated with behavioral depression. Chronic changes in diet composition producing high leptin levels or rLeptin treatment may result in an altered response to cocaine in ethologic tests that measure degrees of anxiety and depression, which could be attributed to an antagonistic effect of leptin.

Ataques de pânico provocados pelo dióxido de carbono: etiopatogenia, bloqueio através de psicofármacos e terapia cognitivo-comportamental / Carbon dioxide induced panics attacs: ethiopathogeny, blockade by psychopharmacologic drugs and behavior therapy

Os efeitos ansiogênicos do dióxido de carbono säo maiores em pacientes com transtorno do pânico do que em controles normais. A verificaçäo do efeito ansiolítico do tratamento com drogas pode esclarecer a importância da ansiedade induzida pelo CO2 para a fisiologia de estados naturais de ansiedade. Os principais mecanismos etiopatogênicos responsáveis pelo dióxido de carbono parecem estar associados a: 1. variaçöes bruscas de pH cerebral, 2. estimulaçäo do locus ceruleus, 3. mecanismos serotoninérgicos, 4. teoria do alarme de falsa sufocaçåo, 5. fatores cognitivos, 6. níveis de ansiedade pré-teste, 7. fatores genéticos. Através da revisäo bibliográfica, destacamos todos os estudos que utilizaram psicofármacos e terapia cognitivo-comportamental com finalidade de bloquear ou atenuar ataques de pânico induzidos pelo dióxido de carbono. Para isto foi utilizado o sistema MEDLINE (1980 a 1999). As palavras-chaves utilizadas foram: ataque de pânico, transtorno do pânico, dióxido de carbono, drogas tricíclicas, inibidores de monoamino-oxidase, fluoxetina, paroxetina, sertralina, fluvoxamina. As referências dos artigos encontrados também foram examinadas. Os testes de induçäo de ataques de pânico com dióxido de carbono podem ser instrumentos úteis para seleçäo de drogas psicotrópicas com propriedades antipânico

Effect of phenobarbitone administration to pregnant rats on anxiety in offsprings.

Adults Charles-Foster rats were prenatally treated to phenobarbitone (10 mg/kg, i.p.) from day 13 to 21 of gestation, this being the critical period of neural development. Pregnant control rats were similarly treated with equal volume of vehicle. Adult rat offsprings at 8-9 weeks of age were subjected to open-field exploratory behaviour, elevated plus-maze and elevated zero-maze tests. The rat offsprings displayed significantly increased ambulation and rearings in an open-field arena when compared to control offsprings whereas self-grooming and faecal droppings remain unchanged. On elevated plus-maze test these prenatally treated rat offsprings spent significantly less time on open arms and more time and more number of entries in enclosed arms as compared to controls. Prenatally exposed rats also showed significant less time on open arms, less number of head dips and stretched attend postures on elevated zero-maze test indicating increased anxiogenic behavioural pattern in these animals. The results suggest that prenatal exposure to phenobarbitone leaves a lasting effect on the anxiety state of the offsprings.

A comparative study of anxiogenic effects of fluoroquinolones in rats.

The present study compares the anxiogenic effects of three fluoroquinolones namely ciprofloxacin, ofloxacin and pefloxacin in rats using elevated plus-maze. The rats were treated with 12.5 mg/kg and 25 mg/kg of ciprofloxacin, ofloxacin or pefloxacin and then tested in elevated plus-maze half an hour later, for a period of 5 min. All the three fluoroquinolones decreased the time spent in open arm considerably. This decrease was statistically significant only with the higher doses of ciprofloxacin and ofloxacin (P < 0.05). Mean time spent in closed arm was increased by all the test drugs in both the doses. Increase was statistically significant with both the doses of ofloxacin (P < 0.05). Mean time spent in closed arm was increased by all the test drugs in both the doses. Increase was statistically significant with both the doses of ofloxacin (P < 0.05, P < 0.01 respectively) and higher doses of ciprofloxacin and pefloxacin (P < 0.01, P < 0.05 respectively). The number of entries in open arm and closed arm were decreased by both the doses of the three fluoroquinolones used in the study. The reduction in total number of arm entries by ciprofloxacin, ofloxacin and pefloxacin in both the doses was highly significant. The results suggest definite anxiogenic potential of fluoroquinolones.

Effects of some anxiogenic agents on rat brain monoamine oxidase (MAO) A and B inhibitory (tribulin) activity.

Anxiogenic agents, yohimbine, pentylenetetrazole (PTZ), quinine, bufotenine, flumazenil and isatin were administered (ip) to rats at doses known to induce anxiety in this species. All the drugs exhibited anxiogenic response on the elevated plus-maze and induced a parallel increase in endogenous brain monoamine oxidase (MAO) inhibitory (tribulin) activity. The intensity of the drug-induced anxiety was fairly well correlated with the magnitude of increase in the MAO A inhibitory component of tribulin but not so with its MAO B inhibitory component. Thus, in the doses used, the degree of anxiogenic activity was PTZ > yohimbine > bufotenine > quinine > isatin > flumazenil, in terms of % entries on the open arms of the maze, whereas the magnitude of endogenous MAO A inhibition was PTZ > yohimbine > bufotenine > quinine > flumazenil > isatin. The results indicate that the MAO A inhibitory component of tribulin, rather than its MAO B inhibitory component, may be responsible for the postulated function of tribulin as an endogenous marker of anxiety.

Behavioural effects of prenatal diazepam administration on anxiety patterns in rats.

Diazepam (10 mg/kg, ip) treatment was given from day 13 to 20 of gestation to pregnant rats, this being the critical period for neural development in this species. The pups born were subjected to open-field exploratory behaviour, tunnel-board exploratory behaviour, elevated zero maze behaviour and social interaction tests at 8-9 weeks of age. The results indicate that prenatal diazepam treatment induces a significant increase in open-field ambulation, grooming, scratching and licking/washing, whereas rearing and faecal dropping remain unchanged. Significant reduction in tunnel-board exploratory activity, activity on zero-maze and social interaction were also observed in the prenatally diazepam treated offsprings. The results suggests that prenatal interference in the form of diazepam leaves a lasting imprint on offsprings resulting in hyper-emotional responsiveness and anxiety state.

Distinct grooming patterns induced by intracerebroventricular injection of CRH, TRH and LHRH in male rats

This paper reports the effects on grooming, related behaviors and levels of anxiety induced by the hypophysiotropic peptides corticotropin-releasing hormone (CRH, 1 mug, 0.2 nmol, icv), thyrotropin-releasing hormone (TRH, 100 mug, 275 nmol, icv) and luteinizing hormone-releasing hormone (LHRH, 1.5 mug, 1.3 nmol, icv) administered into the lateral ventricle of the brain (icv) of adult male rats of a Holtzman-derived colony (N = 15, each group). CRH induced an increase in total grooming scores, whereas LHRH, TRH and vehicle had no effect. CRH strongly increased face and head grooming and induced head shakes. The time spent in rearing and gnawing was significantly decreased. In the plus-maze, CRH reduced the time of exploration in the open arm. TRH increased face grooming and induced body shakes. LHRH had no effect on grooming or rearing behavior. No body or head shakes were observed after LHRH administration. Scoring of individual grooming elements demonstrated differences in action of the three peptides. Although both CRH and TRH increased face grooming, only CRH induced head grooming. Furthermore, CRH induced predominantly head shakes while TRH increased body shake activity. In contrast, CRH was anxiogenic and TRH appeared to induce stereotyped behavior. From the characterization of grooming elements and related responses, we conclude that each hypophysiotropic peptide induces a specific behavioral pattern.

Protective effect of BR-16A (Mentat), a herbal preparation on alcohol abstinence-induced anxiety and convulsions.

Chronic administration of ethanol (2-5 g/kg, po) on days 1 to 6 and its withdrawal produced anxiogenic reaction in mice and rats as assessed on the elevated plus-maze. Daily administration of BR-16A (100 mg/kg) prior to ethanol intoxication for 6 days prevented withdrawal induced anxiety in both rats and mice. However, acute administration of a single dose of BR-16A, to animals withdrawn from ethanol, i.e. on the 7th day, showed significant anxiogenic response. Ethanol withdrawal also sensitized the convulsogenic reaction to pentylenetetrazole (PTZ). A non-convulsive dose (40 or 60 mg/kg) of PTZ produced full blown convulsions and increased mortality in ethanol withdrawn rats and mice, respectively. Both acute and chronic administration of BR-16A (100 mg/kg) exhibited significant protection against ethanol withdrawal-induced reduction in PTZ threshold in rats and mice. The results suggest the usefulness of this safe herbal psychotropic preparation in the management of ethanol withdrawal reactions.