New insights on amygdala : basomedial amygdala regulates the physiological response to social novelty.

The amygdala has been associated with a variety of functions linked to physiological, behavioral and endocrine responses during emotional situations. This brain region is comprised of multiple sub-nuclei. These subnuclei belong to the same structure, but may be involved in different functions, thereby making the study of each sub-nuclei important. Yet, the involvement of the basomedial amygdala (BMA) in the regulation of emotional states has yet to be defined. Therefore, the aim of our study was to investigate the regulatory role of the BMA on the responses evoked during a social novelty model and whether the regulatory role depended on an interaction with the dorsomedial hypothalamus (DMH). Our results showed that the chemical inhibition of the BMA by the microinjection of muscimol (c-aminobutyric acid (GABAA) agonist) promoted increases in mean arterial pressure (MAP) and heart rate (HR), whereas the chemical inhibition of regions near the BMA did not induce such cardiovascular changes. In contrast, the BMA chemical activation by the bilateral microinjection of bicuculline methiodide (BMI; GABAA antagonist), blocked the increases in MAP and HR observed when an intruder rat was suddenly introduced into the cage of a resident rat, and confined to the small cage for 15 min. Additionally, the increase in HR and MAP induced by BMA inhibition were eliminated by DMH chemical inhibition. Thus, our data reveal that the BMA is under continuous GABAergic influence, and that its hyperactivation can reduce the physiological response induced by a social novelty condition, possibly by inhibiting DMH neurons

Tobacco-free cigarette smoke exposure induces anxiety and panic-related behaviours in male wistar rats.

Smokers, who generally present with lung damage, are more anxious than non-smokers and have an associated augmented risk of panic. Considering that lung damage signals specific neural pathways that are related to affective responses, the aim of the present study was to evaluate the influence of pulmonary injury on anxiety and panic-like behaviours in animals exposed to cigarette smoke with and without tobacco. Male Wistar rats were divided into the following groups: a control group (CG); a regular cigarette group (RC); and a tobacco-free cigarette (TFC) group. Animals were exposed to twelve cigarettes per day for eight consecutive days. The animals were then exposed to an elevated T-maze and an open field. The RC and TFC groups presented increases in inflammatory cell inflow, antioxidant enzyme activity, and TBARS levels, and a decrease in the GSH/GSSG ratio was observed in the TFC group. Exposure to RC smoke reduced anxiety and panic-related behaviours. On the other hand, TFC induced anxiety and panic-related behaviours. Thus, our results contradict the concept that nicotine is solely accountable for shifted behavioural patterns caused by smoking, in that exposure to TFC smoke causes anxiety and panic-related behaviours.Cigarette smoke exposure is associated with anxiety states. Smokers are more anxious than non-smokers1, while cigarette smoking cessation is associated with increased levels of anxiety and stress, as the nicotine in cigarettes has been shown to have anxiolytic effects2. Moreover, smoking is also associated with an augmented risk of panic attacks, and quitting smoking could help reduce this risk3. Importantly, in a study conducted by Amaring and colleagues, it was reported that 72% of panic disorder patients declared that they were regular smokers at the onset of their disease4. Cigarette smoke is also one of the several agents and environmental factors that can trigger oxidative stress and pulmonary damage5. Cigarette smoke causes cellular recruitment, lipid peroxidation, production of inflammatory mediators, and oxidative stress6?11. For instance, studies in mice have shown that exposure to short-term cigarette smoke evokes an increase in inflammatory cell inflow and oxidative damage6,9. In general, exposure to pollutants induces pulmonary inflammation through the generation of oxidative stress12,13, defined as the imbalance in reactive oxygen species production, to the detriment of the antioxidant defence systems14. Importantly, exposure to ambient air particles not only induces pulmonary inflammation but also behavioural disorders both in humans and in mice15. Currently, the majority of anxiety studies associated with cigarette smoking have focused on the anxiolytic effects of nicotine2. However, it has been shown that lung damage can induce central nervous system responses by activating specific neuronal pathways16,17, which include those linked to affective responses, such as anxiety and panic18. This raises the question of whether the anxiety and panic-type behaviour associated with smoking might be related not only to the nicotine or to tobacco?s other constituents but also to lung damage

Relação entre a obesidade induzida por dieta hiperlipídica e o desenvolvimento de transtornos de ansiedade em ratos Wistar.

Programa de Pós-Graduação em Ciências Biológicas. Núcleo de Pesquisas em Ciências Biológicas, Pró-Reitoria de Pesquisa de Pós Graduação, Universidade Federal de Ouro Preto.As alterações nos padrões alimentares decorrentes do aumento no consumo de gordura satura estão fortemente relacionadas ao avanço da prevalência de obesidade, ganho de peso e acúmulo de tecido adiposo branco visceral (TAB). Estas alterações fisiologicas vem sendo amplamente associadas ao desenvolvimento de psicopatologias que englobam a disfunção cognitiva, estresse pscicológico crônico, depressão e transtornos de ansiedade. O processo inflamatório desencadeado pela obesidade em tecidos periféricos atinge também diferentes núcleos do SNC, levando ao desenvolvimento de neuroinflamação de diferentes núcleos, como o hipotalâmico dorsomedial (HDM). Estudos demonstram que o HDM é tônicamente regulado por projeções excitatórias glutamatérgicas e projeções inibitórias GABAérgicas e que este está intimamente envolvido no controle da reatividade cardiovascular ao estresse emocional, participando também das respostas comportamentais de roedores. O objetivo deste trabalho foi investigar as alterações comportamentais de esquiva inibitória e fuga, em animais induzidos à obesidade por dieta hiperlipídica (DH; 45% de gordura), por 9 semanas. As alterações comportamentais dos grupos DC e DH foram avaliadas pelo modelo comportamental no Labirinto em T-elevado (LTE), que consiste em expor os animais no braço fechado (3 tentativas), seguida por exposição ao braço aberto (3 tentativas). Estudos associam a esquiva inibitória ao comportamento do tipo ansiedade, e este é analisado com base no tempo que o animal gasta para sair do braço fechado em cada tentativa. A fuga vem sendo associada ao comportamento do tipo pânico, que é analisada com base no tempo que o animal gasta para deixar o braço aberto. Os animais foram tratados com veículo (PBS), muscimol (agonista GABAA) e bicuculina methiodide (BMI) (antagonista GABAA) antes do teste no LTE. Demonstramos que o grupo obeso veículo apresenta comportamento do tipo ansiedade, com aumento na latência de esquiva quando expostos ao braço fechado do LTE, mas não apresentaram comportamento do tipo pânico. O muscimol não foi eficiente em reduzir a latência de esquiva, mas foi capaz de aumentar a latência de fuga no braço aberto, sugerindo um efeito panicolítico desta droga. A BMI não foi capaz de alterar o comportamento de fuga, mas aumentou a latência de esquiva e comprometeu o aprendizado no grupo controle. Este efeito da BMI não foi observado nos animais obesos, reforçando a idéia de que a obesidade induzida por DH compromete o tônus GABAérgico no HDM.Changes on eating patterns resulting from high consumption of saturated fat are strongly related to the prevalence of obesity and increased visceral white adipose tissue, which is an important risk factor in the development of comorbidities, among them cognitive dysfunction, chronic lack of psychic stress, hypothalamic inflammation, depression and anxiety disorders. Obesity compromises the regulation of brain nuclei, among them, the dorsomedial hypothalamus (DMH). It is known that the HDM is regulated by tonically glutamatergic excitatory projections and inhibitory GABAergic projections, which are involved in the control of cardiovascular reactivity to stress, as well as behavioral regulation and states of anxiety disorders. The aim of this study was to investigate the behavioral changes related to anxiety-like and panic-like disorders in animals fed a high-fat diet for nine weeks that induced-obesity (HFD 45% fat). For this, we evaluated the behavioral pattern of obese and control animals in the Elevated T-Maze (ETM). This test consists of exposing the animals in the enclosed arm (3 trials) followed by exposure to the open arm (3 trials). The anxiety-like behavior are correlated to time latency that the animal spends to withdrawl from the enclosed arm on each trial, and the panic-like behavior is correlated to time latency that animal takes to leave the open arm. The animals were treat with vehicle (PBS), muscimol (GABAA agonist) or bicuculline methiodide (GABAA antagonist) before the test in ETM. Our results showed that the obese animals (treated with vehicle) have an anxiety-like behavior evidenced by increased time latency in the enclosed arm of the apparatus, when compared to control animals, however, those animals showed no panic-like behavior. We also observed that muscimol was not effective in reducing the anxiety-like behavior, but showed a potential panicolytic action by increasing the time latency spent by animals in the open arm of the ETM. Treatment with BMI was not effective by inducing panic-like behavior in animals. However, the control group was induce to anxiety-like behavior and had impaired learning ability, an effect that was not observe in obese animals treated with BMI when compared to obese vehicle group, which confirms the involvement of GABAergic commitment in HDM of these animals

High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats.

Overweight and obesity are conditions associated with an overall range of clinical health consequences, and they could be involved with the development of neuropsychiatric diseases, such as generalized anxiety disorder (GAD) and panic disorder (PD). A crucial brain nuclei involved on the physiological functions and behavioral responses, especially fear, anxiety and panic, is the dorsomedial hypothalamus (DMH). However, the mechanisms underlying the process whereby the DMH is involved in behavioral changes in obese rats still remains unclear. The current study further investigates the relation between obesity and generalized anxiety, by investigating the GABAA sensitivity to pharmacological manipulation within the DMH in obese rats during anxiety conditions. Male Wistar rats were divided in two experimental groups: the first was fed a control diet (CD; 11% w/w) and second was fed a high fat diet (HFD; 45% w/w). Animals were randomly treated with muscimol, a GABAA agonist and bicuculline methiodide (BMI), a GABAA antagonist. Inhibitory avoidance and escape behaviors were investigated using the Elevated T-Maze (ETM) apparatus. Our results revealed that the obesity facilitated inhibitory avoidance acquisition, suggesting a positive relation between obesity and the development of an anxiety-like state. The injection of muscimol (an anxiolytic drug), within the DMH, increased the inhibitory avoidance latency in obese animals (featuring an anxiogenic state). Besides, muscimol prolonged the escape latency and controlling the possible panic-like behavior in these animals. Injection of BMI into the DMH was ineffective to produce an anxiety-like effect in obese animals opposing the results observed in lean animals. These findings support the hypotheses that obese animals are susceptible to develop anxiety-like behaviors, probably through changes in the GABAergic neurotransmission within the DMH

Estrogen receptor ? activation within dorsal raphe nucleus reverses anxiety-like behavior induced by food restriction in female rats.

Severe food restriction (FR), as observed in disorders like anorexia nervosa, has been associated to the reduction of estrogen levels, which in turn could lead to anxiety development. Estrogen receptors, mainly ER? type, are commonly found in the dorsal raphe nucleus (DRN) neurons, an important nucleus related to anxiety modulation and the primary source of serotonin (5-HT) in the brain. Taking together, these findings suggest an involvement of estrogen in anxiety modulation during food restriction, possibly mediated by ER? activation in serotonergic DRN neurons. Thus, the present study investigated the relationship between food restriction and anxiety-like behavior, and the involvement of DRN and ER? on the modulation of anxiety-like behaviors in animals subjected to FR. For that, female Fischer rats were grouped in control group, with free access to food, or a FR group, which received 40% of control intake during 14 days. Animals were randomly treated with 17?-estradiol (E2), DPN (ER? selective agonist), or their respective vehicles, PBS and DMSO. Behavioral tests were performed on Elevated T-Maze (ETM) and Open Field (OF). Our results suggest that FR probably reduced the estrogen levels, since the remained in the non-ovulatory cycle phases, and their uterine weight was lower when compared to control group. The FR rats showed increased inhibitory avoidance latency in theETM indicating that FR is associated with the development of an anxiety-like state. The injections of both E2 and DPN into DRN of FR animals had an anxiolytic effect. Those data suggest thatanxiety-like behavior induced by FR could be mediated by a reduction of ER? activation in the DRN neurons, probably due to decreased estrogen levels

Association of high-fat diet with neuroinflammation, anxiety-like defensive behavioral responses, and altered thermoregulatory responses in male rats.

Overweight and obesity are a worldwide pandemic affecting billions of people. These conditions have been associated with a chronic low-grade inflammatory state that is recognized as a risk factor for a range of somatic diseases as well as neurodevelopmental disorders, anxiety disorders, trauma- and stressor-related disorders, and affective disorders. We previously reported that the ingestion of a high-fat diet (HFD; 45% fat kcal/g) for nine weeks was capable of inducing obesity in rats in association with increased reactivity to stress and increased anxiety-related defensive behavior. In this study, we conducted a nine-week diet protocol to induce obesity in rats, followed by investigation of anxiety-related defensive behavioral responses using the elevated T-maze (ETM), numbers of FOS-immunoreactive cells after exposure of rats to the avoidance or escape task of the ETM, and neuroinflammatory cytokine expression in hypothalamic and amygdaloid nuclei. In addition, we investigated stress-induced cutaneous thermoregulatory responses during exposure to an open-field (OF). Here we demonstrated that nine weeks of HFD intake induced obesity, in association with increased abdominal fat pad weight, increased anxiety-related defensive behavioral responses, and increased proinflammatory cytokines in hypothalamic and amygdaloid nuclei. In addition, HFD exposure altered avoidance- or escape task-induced FOSimmunoreactivity within brain structures involved in control of neuroendocrine, autonomic, and behavioral responses to aversive stimuli, including the basolateral amygdala (BLA) and dorsomedial (DMH), paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei. Furthermore, rats exposed to HFD, relative to control dietfed rats, responded with increased tail skin temperature at baseline and throughout exposure to an open-field apparatus. These data are consistent with the hypothesis that HFD induces neuroinflammation, alters excitability of brain nuclei controlling neuroendocrine, autonomic, and behavioral responses to stressful stimuli, and enhances stress reactivity and anxiety-like defensive behavioral responses

Tobacco-Free Cigarette Smoke Exposure Induces Anxiety and Panic-Related Behaviours in Male Wistar Rats

Abstract Smokers, who generally present with lung damage, are more anxious than non-smokers and have an associated augmented risk of panic. Considering that lung damage signals specific neural pathways that are related to affective responses, the aim of the present study was to evaluate the influence of pulmonary injury on anxiety and panic-like behaviours in animals exposed to cigarette smoke with and without tobacco. Male Wistar rats were divided into the following groups: a control group (CG); a regular cigarette group (RC); and a tobacco-free cigarette (TFC) group. Animals were exposed to twelve cigarettes per day for eight consecutive days. The animals were then exposed to an elevated T-maze and an open field. The RC and TFC groups presented increases in inflammatory cell inflow, antioxidant enzyme activity, and TBARS levels, and a decrease in the GSH/GSSG ratio was observed in the TFC group. Exposure to RC smoke reduced anxiety and panic-related behaviours. On the other hand, TFC induced anxiety and panic-related behaviours. Thus, our results contradict the concept that nicotine is solely accountable for shifted behavioural patterns caused by smoking, in that exposure to TFC smoke causes anxiety and panic-related behaviours