Tryptophan overloading activates brain regions involved with cognition, mood and anxiety

ABSTRACT Tryptophan is the only precursor of serotonin and mediates serotonergic activity in the brain. Previous studies have shown that the administration of tryptophan or tryptophan depletion significantly alters cognition, mood and anxiety. Nevertheless, the neurobiological alterations that follow these changes have not yet been fully investigated. The aim of this study was to verify the effects of a tryptophan-enriched diet on immunoreactivity to Fos-protein in the rat brain. Sixteen male Wistar rats were distributed into two groups that either received standard chow diet or a tryptophan-enriched diet for a period of thirty days. On the morning of the 31st day, animals were euthanized and subsequently analyzed for Fos-immunoreactivity (Fos-ir) in the dorsal and median raphe nuclei and in regions that receive serotonin innervation from these two brain areas. Treatment with a tryptophan-enriched diet increased Fos-ir in the prefrontal cortex, nucleus accumbens, paraventricular hypothalamus, arcuate and ventromedial hypothalamus, dorsolateral and dorsomedial periaqueductal grey and dorsal and median raphe nucleus. These observations suggest that the physiological and behavioral alterations that follow the administration of tryptophan are associated with the activation of brain regions that regulate cognition and mood/anxiety-related responses.

Imbalance in the diurnal salivary testosterone/cortisol ratio in men with severe obstructive sleep apnea: an observational study / Desequilíbrio na proporção salivar diurna de testosterona/cortisol em homens com apneia obstrutiva do sono grave: um estudo observacional

ABSTRACT INTRODUCTION: The complex relationship between sleep disorders and hormones could lead to alterations in the production of cortisol and testosterone in obstructive sleep apnea (OSA) patients. OBJECTIVE: The purpose of this study was to determine the diurnal trajectories of salivary free-testosterone, free-cortisol and their ratio (T/C). METHODS: Ten subjects newly diagnosed with OSA, based on nocturnal polysomnography evaluation and excessive daytime sleepiness, and seven matched controls were consecutively recruited. Cortisol and testosterone were measured in salivary samples collected upon awakening, at noon and in the evening. The psychometric evaluation of anxiety/depression and referred sexual function disturbances was performed to evaluate the presence of neuropsychological comorbidities. RESULTS AND CONCLUSION: The main finding was that OSA subjects displayed hypocortisolism upon awakening and a significant reduction in testosterone concentration in the evening in comparison with the control group, which has maintained the physiological testosterone and cortisol diurnal fluctuation, with higher hormone concentrations in the morning and lower concentrations in the evening. The use of data from multiple diurnal measurements rather than a single point allowed the detection of T/C ratio changes of opposite signs at the beginning and end of the day: the OSA subjects had a higher T/C ratio than the controls in the morning, while their T/C ratio was significantly lower than that of the controls in the evening. The imbalances in the anabolic-catabolic diurnal equilibrium suggest that OSA is associated with a dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, potentially an underlying cause of some of the neuropsychological comorbidities observed in OSA patients.

Resumo Introdução: A relação complexa entre os distúrbios do sono e os hormônios pode levar a alterações na produção de cortisol e testosterona em pacientes com Apneia obstrutiva do sono (AOS). Objetivo: O objetivo deste estudo foi determinar as curvas diurnas de testosterona e cortisol livres na saliva e sua proporção (razão T/C). Método: Dez indivíduos recém-diagnosticados com AOS com base na avaliação por polissonografia noturna e sonolência diurna excessiva e sete controles pareados foram recrutados, consecutivamente. Cortisol e testosterona foram medidos em amostras de saliva coletadas ao acordar, ao meio-dia e à noite. A avaliação psicométrica dos distúrbios de ansiedade/depressão e função sexual mencionados foi realizada para detectar a presença de comorbidades neuropsicológicas. Resultados: O achado principal foi que os indivíduos com AOS apresentam hipocortisolismo ao acordar e uma redução significante na concentração de testosterona à noite, em comparação com o grupo controle, que manteve a variação fisiológica diurna de testosterona e cortisol com concentrações hormonais mais elevadas pela manhã e concentrações mais baixas durante a noite. O uso de dados de várias mensurações diurnas, em vez de uma única mensuração, permitiu detectar as alterações na razão T/C de sinais opostos no início e no final do dia: os indivíduos com AOS apresentaram razão T/C maior que os controles na parte da manhã, enquanto que a razão T/C foi significantemente inferior à dos controles durante a noite. Conclusão: Os desequilíbrios no balanço anabólico-catabólico diurno sugerem que a AOS está associada a uma desregulação dos eixos hipotálamo-hipófise-adrenal e hipotálamo-hipófise-gonadal, potencialmente a causa subjacente de algumas das comorbidades neuropsicológicas observadas em pacientes com AOS.

Activation of locus coeruleus heme oxygenase-carbon monoxide pathway promoted an anxiolytic-like effect in rats

The heme oxygenase-carbon monoxide pathway has been shown to play an important role in many physiological processes and is capable of altering nociception modulation in the nervous system by stimulating soluble guanylate cyclase (sGC). In the central nervous system, the locus coeruleus (LC) is known to be a region that expresses the heme oxygenase enzyme (HO), which catalyzes the metabolism of heme to carbon monoxide (CO). Additionally, several lines of evidence have suggested that the LC can be involved in the modulation of emotional states such as fear and anxiety. The purpose of this investigation was to evaluate the activation of the heme oxygenase-carbon monoxide pathway in the LC in the modulation of anxiety by using the elevated plus maze test (EPM) and light-dark box test (LDB) in rats. Experiments were performed on adult male Wistar rats weighing 250-300 g (n=182). The results showed that the intra-LC microinjection of heme-lysinate (600 nmol), a substrate for the enzyme HO, increased the number of entries into the open arms and the percentage of time spent in open arms in the elevated plus maze test, indicating a decrease in anxiety. Additionally, in the LDB test, intra-LC administration of heme-lysinate promoted an increase on time spent in the light compartment of the box. The intracerebroventricular microinjection of guanylate cyclase, an sGC inhibitor followed by the intra-LC microinjection of the heme-lysinate blocked the anxiolytic-like reaction on the EPM test and LDB test. It can therefore be concluded that CO in the LC produced by the HO pathway and acting via cGMP plays an anxiolytic-like role in the LC of rats.

Dyspeptic symptoms in patients with type 1 diabetes: endoscopic findings, Helicobacter pylori infection, and associations with metabolic control, mood disorders and nutritional factors

Objectives To evaluate, in a group of patients with long-standing type 1 diabetes (DM1), an association of dyspepsia symptoms with: changes in the gastroduodenal mucosa, infection by Helicobacter pylori, glycemic control, and psychological and nutritional factors. Subjects and methods A total of 32 patient with DM1 were studied (age: 38 ± 9 years; females: 25; diabetes duration: 22 ± 5 years). All patients answered a standardized questionnaire for the evaluation of gastrointestinal symptoms and underwent upper gastrointestinal endoscopy, with gastric biopsies for the evaluation of Helicobacter pylori infection. The presence of anxiety and depression was evaluated by the HAD scale. Nutritional parameters were BMI, arm and waist circumference, skinfold measurement, and body fat percentage. Results Upper endoscopy detected lesions in the gastric mucosa in 34.4% of the patients, with similar frequency in those with (n = 21) and without dyspepsia (n = 11). The patients with dyspepsia complaints showed greater frequency of depression (60% vs. 0%; p = 0.001), higher values for HbA1c (9.6 ± 1.7 vs. 8.2 ± 1.3%; p = 0.01) and lower values for BMI (24.3 ± 4.1 vs. 27.2 ± 2.6 kg/m2; p = 0.02), body fat percentage (26.6 ± 6.2 vs. 30.8 ± 7.7%; p = 0.04), and waist circumference (78.7 ± 8 vs. 85.8 ± 8.1 cm; p = 0.02). No association was found between the symptoms and the presence of Helicobacter pylori. Conclusions Dyspepsia symptoms in patients with long-standing DM1 were associated with glycemic control and depression, and they seem to negatively influence the nutritional status of these patients. .

Estrous cycle and stress: influence of progesterone on the female brain

The female brain operates in a constantly changing chemical milieu caused by cyclical changes in gonadal hormones during the estrous cycle (menstrual cycle in women). Such hormones are highly lipophilic and pass readily from the plasma to the brain where they can influence neuronal function. It is becoming clear that the rapid reduction in peripheral circulating progesterone, which occurs during the late diestrous phase of the cycle, can trigger a withdrawal-like response, in which changes in GABA A receptor expression render hyper-responsive certain brain areas involved in processing responses to stressful stimuli. The periaqueductal gray matter (PAG) is recognised as an important region for integrating anxiety/defence responses. Withdrawal from progesterone, via actions of its neuroactive metabolite allopregnanolone, triggers up-regulation of extrasynaptic GABA A receptors on GABAergic neurons in the PAG. As a consequence, ongoing GABAergic tone on the output cells decreases, leading to an increase in functional excitability of the circuitry and enhanced responsiveness to stressful stimuli during the late diestrous phase. These changes during late diestrus could be prevented by short-term neurosteroid administration, timed to produce a more gradual fall in the peripheral concentration of allopregnanolone than the rapid decrease that occurs naturally, thus removing the trigger for the central withdrawal response.

Fine-tuning of defensive behaviors in the dorsal periaqueductal gray by atypical neurotransmitters

This paper presents an up-to-date review of the evidence indicating that atypical neurotransmitters such as nitric oxide (NO) and endocannabinoids (eCBs) play an important role in the regulation of aversive responses in the periaqueductal gray (PAG). Among the results supporting this role, several studies have shown that inhibitors of neuronal NO synthase or cannabinoid receptor type 1 (CB1) receptor agonists cause clear anxiolytic responses when injected into this region. The nitrergic and eCB systems can regulate the activity of classical neurotransmitters such as glutamate and γ-aminobutyric acid (GABA) that control PAG activity. We propose that they exert a ‘fine-tuning’ regulatory control of defensive responses in this area. This control, however, is probably complex, which may explain the usually bell-shaped dose-response curves observed with drugs that act on NO- or CB1-mediated neurotransmission. Even if the mechanisms responsible for this complex interaction are still poorly understood, they are beginning to be recognized. For example, activation of transient receptor potential vanilloid type-1 channel (TRPV1) receptors by anandamide seems to counteract the anxiolytic effects induced by CB1 receptor activation caused by this compound. Further studies, however, are needed to identify other mechanisms responsible for this fine-tuning effect.

Hypoxic-ischemic injury decreases anxiety-like behavior in rats when associated with loss of tyrosine-hydroxylase immunoreactive neurons of the substantia nigra

Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time) on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra (SN). The mild and severe HI groups were exposed to hypoxia (8 percent O2/92 percent N2) for 90 and 150 min, respectively. The elevated plus-maze (EPM) test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT) and OAT percent, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT percent in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05). The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2 percent) and severe HI groups (16.3, 32.2, and 43.8 percent, respectively; P < 0.05). The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.

Involvement of β3-adrenergic receptors in the control of food intake in rats

This study examined the food intake changes evoked by intracerebroventricular (icv) injection of a selective agonist (BRL37344, 2 and 20 nmol) or antagonist (SR59230A, 10 and 50 nmol) of β3-adrenergic receptors in 24-h fasted rats (adult male Wistar rats, 200-350 g, N = 6/treatment). The animals were also pretreated with saline icv (SAL) or SR59230A (50 nmol) followed by BRL37344 (20 nmol) or SAL in order to determine the selectivity of the effects evoked by BRL37344 on food intake or the selectivity of the effects evoked by SR59230A on risk assessment (RA) behavior. The highest dose of BRL37344 (N = 7) decreased food intake 1 h after the treatment (6.4 ± 0.5 g in SAL-treated vs 4.2 ± 0.8 g in drug-treated rats). While both doses of SR59230A failed to affect food intake (5.1 ± 1.1 g for 10 nmol and 6.0 ± 1.8 g for 50 nmol), this treatment reduced the RA frequency (number/30 min) (4 ± 2 for SAL-treated vs 1 ± 1 for 10 nmol and 0.5 ± 1 for 50 nmol SR59230A-treated rats), an ethological parameter related to anxiety. While pretreatment with SR59230A (7.0 ± 0.5 g) abolished the hypophagia induced by BRL37344 (3.6 ± 0.9 g), BRL37344 suppressed the reduction in RA frequency caused by SR59230A. These results show that the hypophagia caused by BRL37344 is selectively mediated by β3-adrenergic receptors within the central nervous system. Moreover, they suggest the involvement of these receptors in the control of anxiety.

Midazolam oral como medicação pré-anestésica em blefaroplastias / Oral sedation with midazolam in blepharoplasty

OBJETIVO: Avaliar a eficácia e a segurança do emprego oral de midazolam (15 mg) como medicação pré-anestésica em pacientes submetidos a blefaroplastias. MÉTODOS: Foi desenvolvido um ensaio clínico prospectivo, duplo cego, randomizado, controlado com 42 pacientes, risco ASA I e II, divididos em três grupos de 14 pacientes: grupo M (midazolam 15 mg), grupo P (placebo) e grupo SM (sem medicação). Os pacientes foram avaliados quanto ao grau de sedação e dor intraoperatórias e variação entre os períodos pré e transoperatórios da ansiedade, pressão arterial sistólica e diastólica, frequência respiratória e pulso. RESULTADOS: A análise de variância unifatorial com teste de Tukey mostrou que a administração de midazolam ocasionou uma redução significativa da pressão arterial sistólica e da frequência respiratória no período transoperatório em relação aos pacientes que utilizaram placebo ou não fizeram uso de medicamento. Esses efeitos foram discretos e acompanhados de diminuição na percepção da dor, discreta sedação e redução da ansiedade. CONCLUSÃO: A sedação via oral com midazolam em pacientes submetidos a cirurgias palpebrais demonstrou ser eficiente de fácil aplicação e com mínimos efeitos sistêmicos.

PURPOSE: To evaluate the safety and usefulness of the use of oral sedation with midazolam (15 mg) in patients submitted to blepharoplasty. METHODS: Randomized double-blind prospective study of 42 patients (surgical risk ASA I and II) divided into three groups of 14 patients each: Group M (midazolam 15 mg), group P (placebo) and group SM (no medication). All patients were evaluated according to the degree of sedation and pain during surgery and the variation of anxiety between the preoperative and intraoperative period, arterial pressure (systolic-SAP and diastolic-DAP), respiratory frequency (RF) and pulsation. RESULTS: Unifatorial variance analysis with Tukey test demonstrated that the use of midazolam provoked a significant SAP and RF reduction during the intraoperative period. These effects were not pronounced and were accompanied by a reduction of pain perception and anxiety and mild sedation. CONCLUSIONS: Oral sedation with midazolam in patients that had undergone eyelid surgical procedures is safe and easy to perform with minimal systemic effects.

Changes in the biogenic amine content of the prefrontal cortex, amygdala, dorsal hippocampus, and nucleus accumbens of rats submitted to single and repeated sessions of the elevated plus-maze test

It has been demonstrated that exposure to a variety of stressful experiences enhances fearful reactions when behavior is tested in current animal models of anxiety. Until now, no study has examined the neurochemical changes during the test and retest sessions of rats submitted to the elevated plus maze (EPM). The present study uses a new approach (HPLC) by looking at the changes in dopamine and serotonin levels in the prefrontal cortex, amygdala, dorsal hippocampus, and nucleus accumbens in animals upon single or double exposure to the EPM (one-trial tolerance). The study involved two experiments: i) saline or midazolam (0.5 mg/kg) before the first trial, and ii) saline or midazolam before the second trial. For the biochemical analysis a control group injected with saline and not tested in the EPM was included. Stressful stimuli in the EPM were able to elicit one-trial tolerance to midazolam on re-exposure (61.01 percent). Significant decreases in serotonin contents occurred in the prefrontal cortex (38.74 percent), amygdala (78.96 percent), dorsal hippocampus (70.33 percent), and nucleus accumbens (73.58 percent) of the animals tested in the EPM (P < 0.05 in all cases in relation to controls not exposed to the EPM). A significant decrease in dopamine content was also observed in the amygdala (54.74 percent, P < 0.05). These changes were maintained across trials. There was no change in the turnover rates of these monoamines. We suggest that exposure to the EPM causes reduced monoaminergic neurotransmission activity in limbic structures, which appears to underlie the "one-trial tolerance" phenomenon.

Effects of Preoperative Anxiety on Gastric Fluid Acidity and Volume

The aim of this study was to evaluate the effect of preoperative anxiety on the gastric pH and volume. We studied 96 female patients aged 16-60 yr who underwent elective gynecological surgery. We classified the subjects into 2 groups, those presenting preoperative anxiety scores using visual analogue scale (VAS, 0-10) less than 5 (L-group, n=59), and those with 5 and more (H-group, n=37). Immediately after tracheal intubation, gastric contents were aspirated using a 14-F multiorifice nasogastric tube. The gastric acidity and volume of the two groups were not statistically different. Mean pH were 3.0+/-1.8 and 3.0+/-2.0 in each group (L-group and H-group) and mean gastric volume (mL) were 15.3 +/-11.7 and 11.8 +/-11.8, respectively. Nine (15.3%) patients in the L-group were considered to be 'at risk i.e. gastric pH 25 mL' and one patient (2.7%) in the H-group (p<0.05). The mean serum gastrin concentrations in both groups were similar (21.6+/-9.8 vs. 20.2+/-11.0 pg/mL). The pH and volume of preoperative gastric contents were not correlated with the preoperative anxiety. The results suggest that a low level of preoperative anxiety can be considered a risk factor for aspiration pneumonitis.

Serotonina, matéria cinzenta periaquedutal e transtorno do pânico / Serotonin, periaqueductal gray matter and panic disorder

Este artigo é uma revisäo de evidências experimentais e construtos teóricos que implicam a modulaçäo do comportamento de defesa pela serotonina (5-HT), atuando na matéria cinzenta periaquedutal do mesencéfalo (MCP) no transtorno do pânico. Resultados obtidos com testes de conflito em animais de laboratório indicam que a 5-HT aumenta a ansiedade, enquanto que a estimulaçäo aversiva da MCP aponta para um papel ansiolítico. Para resolver esta contradiçäo, sugeriu-se que os estados emocionais determinados pelos dois paradigmas säo diferentes. Testes de conflito gerariam ansiedade antecipatória, enquanto que a estimulaçäo da MCP produziria medo de perigo iminente. Clinicamente, o primeiro estado estaria relacionado com o transtorno de ansiedade generalizada e o segundo, com o transtorno do pânico. Assim sendo, supöe-se que a 5-HT facilita a ansiedade, porém inibe o pânico. Esta hipótese tem sido testada por meio de um modelo animal de ansiedade e pânico, denominado labirinto em T-elevado, e de dois procedimentos experimentais que geram ansiedade, aplicados tanto em voluntários sadios como em pacientes de pânico. Em geral, os resultados obtidos até agora mostram que drogas que aumentam a açäo da 5-HT elevam diferentes índices de ansiedade, enquanto reduzem índices de pânico. Portanto, as prediçöes baseadas na hipótese em questäo têm se cumprido. As principais implicaçöes clínicas säo as de que um déficit de 5-HT na MCP possa participar da fisiopatogenia do transtorno de pânico e que a intensificaçäo da 5-HT na mesma regiäo medeie a açäo antipânico dos medicamentos antidepressivos

Transmissäo pelo glutamato como alvo molecular na ansiedade / Glutamatergic neurotransmission as molecular target in anxiety

O glutamato (GLU) é o principal neurotransmissor excitatório do cérebro de mamíferos. Os receptores do GLU säo classificados em ionotrópicos ou metabotrópicos. A interferência do GLU no desenvolvimento neural, na plasticidade sináptica, no aprendizado e na memória, na epilepsia, na isquemia neural, na tolerância e na dependência a drogas, na dor neuropática, na ansiedade e na depressäo tem limitado o uso de compostos que agem nos receptores de GLU, quando existe a necessidade de açöes mais seletivas dessas drogas. Dados pré-clínicos em roedores e humanos têm mostrado que compostos que reduzem a ativaçäo do GLU, pelo bloqueio dos seus receptores ou através da reduçäo da sua liberaçäo dos terminais, produzem um perfil ansiolítico em modelos de ansiedade. A aplicaçäo desses compostos em áreas específicas do cérebro, envolvidas na mediaçäo do comportamento defensivo, tal como a substância cinzenta periaquedutal dorsal, também reproduzem o mesmo perfil ansiolítico de açäo. O conhecimento crescente acerca da neurotransmissäo pelo GLU e o desenvolvimento de compostos mais seletivos atuantes nesta neurotransmissäo, renovaram a atençäo para esse sistema neurotransmissor como alvo molecular possível para uma nova classe de drogas no tratamento de condiçöes neuropsiquiátricas. Embora incompleta, esta revisäo tenta atrair a atençäo para a importância de estudos colaborativos entre clínicos e pesquisadores de ciências básicas na geraçäo de idéias para alvos potenciais no desenvolvimento de novos compostos ansiolíticos. e desta maneira contribuir para a compreensäo das bases biológicas da ansiedade

Correlation of serotonin and monoamine oxidase levels with anxiety level in diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is generally considered to have a psychogenic component in its physiopathology. AIM: To study the role of serotonin (5-hydroxytryptamine; 5-HT), monoamine oxidase (MAO) and anxiety, and to elucidate the relationship between these in patients with diarrhea-predominant IBS. METHODS: 5-HT and MAO activity and anxiety levels were studied in 20 healthy volunteers (aged 18-25 years; all men) and 57 patients with diarrhea-predominant IBS (30-60 years; all men). RESULTS: The concentrations of 5-HT (0.3 [0.04] microg/ mL) and MAO (15.5 [3.2] U/mL), and the anxiety level score (14.4 [2.9]) were significantly higher (p < 0.001) in patients than in healthy volunteers (0.1 [0.02], 6.4 [1.4] and 3.4 [1.2], respectively). These parameters correlated with each other in both patients and volunteers. CONCLUSIONS: Elevated 5-HT and MAO activity and anxiety may play a role in patients with diarrhea-predominant IBS.

Relationship of sexuality with psychological and hormonal features in the menopausal period

Women may experience some mental and sexual problems between the ages of 40 years and 60 years due to serious changes in the hormonal system. The aim of this study was to examine the relationships between the changes in sex hormones, sexual behaviours, depression and anxiety levels of women who were in either the premenopausal, perimenopausal or postmenopausal period. The subjects of this cross-sectional study consisted of 324 women who attended the Gynaecology and Obstetrics Out-Patient Ward of Celal Bayar University Hospital. Of this group, 37.0 (n = 124) were postmenopausal, 27.2 (n = 84) perimenopausal and 35.8 (n = 116) premenopausal. Beck Depression Inventory (BDI), State and Trait Anxiety Inventories (STAI-I and II) and a questionnaire on sexual behaviour which was prepared for this study by the authors, were applied to all of the attendees and serum sex hormone levels were analyzed. Beck Depression Anxiety, STAI-I and STAI-II scores and sexual behaviours did not show any statistically significant difference among these three groups. The frequency of sexual intercourse was lower in women with high BDI scores. The rate of painful intercourse was higher in women with high STAI-I scores. The frequency of sexual intercourse, sexual desire and orgasm decreased and painful intercourse increased in women with high STAI-II scores. The frequency of sexual intercourse decreased significantly as the age or follicle stimulating hormone level of women increased. These findings have revealed that the menopausal state did not affect the sexual behaviour, and psychological state of women between the ages of 40 and 60 years, but the increase in anxiety and depression scores affected the sexual life in a negative manner

Serotonin mechanisms in animal models of anxiety

1. Responses to serotonergic drugs in animal models of anxiety are reviewed. Pre- and postsynaptic mechanisms and multiple sites of postsynaptic action contribute to conflicting findings. 2. Paradoxical responses to both serotonergic and non-serotonergic agents support the concept of multiple anxiety mechanisms. Non-anxiety factors, such as effects on cognition and behavioral inhibition, must also be taken into account. 3. Immediate 'anxiogenic' and delayed 'anxiolytic' effects most closely mimic the clinical effects of recently introduced anxiolytic drugs such as the selective serotonin reuptake inhibitors and buspirone. Thus the relevance to anxiety of immediate 'anxiolytic' effects of such agents in animal models is in question