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Anxiety‐related diseases are more than twice as common in women than in men, and in women, symptoms may be exacerbated during the late luteal phase of the menstrual cycle. Despite this, most research into the underlying mechanisms, which drives drug development, have been carried out using male animals. In an effort to redress this imbalance, we compared responses of male and female Wistar rats during exposure to two unconditioned threatening stimuli that evoke panic‐related defensive behaviours: confrontation with a predator (Bothrops alternatus) and acute exposure to hypoxia (7% O2). Threatened by venomous snake, male and female rats initially displayed defensive attention, risk assessment, and cautious interaction with the snake, progressing to defensive immobility to overt escape. Both males and females displayed higher levels of risk assessment but less interaction with the predator. They also spent more time in the burrow, displaying inhibitory avoidance, and more time engaged in defensive attention, and non‐oriented escape behaviour. In females, anxiety‐like behaviour was most pronounced in the oestrous and proestrus phases whereas panic‐like behaviour was more pronounced during the dioestrus phase, particularly during late dioestrus. Acute hypoxia evoked panic‐like behaviour (undirected jumping) in both sexes, but in females, responsiveness in late dioestrus was significantly greater than at other stages of the cycle. The results reveal that females respond in a qualitatively similar manner to males during exposure to naturally occurring threatening stimuli, but the responses of females is oestrous cycle dependent with a significant exacerbation of panic‐like behaviour in the late dioestrus phase. [ABSTRACT FROM AUTHOR]

Neurons in the rat nucleus raphe obscurus (NRO) and nucleus raphe magnus (NRM) were chemically stimulated following electrical stimulation of the periaqueductal gray matter (PAG) to determine if there are afferent pathways that regulate the PAG-mediated cardiovascular defense reaction (CDF), which includes an increase in heart rate, blood pressure, respiration and femoral conductance and reduction in renal conductance. The results indicate that NRO and NRM neurons regulate the CDF by modulating the excitability of neurons of the midbrain defense area, its efferent pathway or both.

Aims: Botulinum toxin A (BTX‐A) is a well‐established treatment for refractory idiopathic overactive bladder (OAB). It has also been used with short‐term success in treating idiopathic urinary retention. However, efficacy and complication rates are variable and predicting those likely to benefit most from treatment would enable personalization of therapy and optimization of outcomes. At the International Consultation on Incontinence‐Research Society (ICI‐RS) meeting in 2019 a Think Tank addressed the question of how we can improve the way we phenotype patients undergoing BTX‐A treatment. Methods: The Think Tank conducted a literature review and expert consensus meeting focussing on how advances in basic science research of the mechanism of action of BTX‐A, as well as assessment of psychological comorbidity, can be translated into clinical practice to improve patient selection for therapy. Results: Idiopathic OAB and idiopathic urinary retention are heterogenous conditions encompassing several phenotypes with multiple potential pathophysiological mechanisms. Animal models have demonstrated a central nervous system mechanism of action of intravesically injected BTX‐A and this has been confirmed in human functional MRI studies, but whether this tool can be used to predict outcome from treatment remains to be determined. Phenotyping based on psychological comorbidity using validated screening tools should be studied as a way to potentially optimize patient selection for therapy. Conclusions: Advances in basic science research into the mechanism of action of BTX‐A have improved our understanding of the pathophysiology of OAB and may lead to novel ways to phenotype patients. Psychological assessment is another way in which phenotyping may be improved. Areas for further research are proposed. [ABSTRACT FROM AUTHOR]

Background: There is a controversy regarding the key role played by opioid peptide neurotransmission in the modulation of panic-attack-related responses.Aims: Using a prey versus rattlesnakes paradigm, the present work investigated the involvement of the endogenous opioid peptide-mediated system of the inferior colliculus in the modulation of panic attack-related responses.Methods: Wistar rats were pretreated with intracollicular administration of either physiological saline or naloxone at different concentrations and confronted with rattlesnakes ( Crotalus durissus terrificus). The prey versus rattlesnake confrontations were performed in a polygonal arena for snakes. The defensive behaviors displayed by prey (defensive attention, defensive immobility, escape response, flat back approach and startle) were recorded twice: firstly, over a period of 15 min the presence of the predator and a re-exposure was performed 24 h after the confrontation, when animals were exposed to the experimental enclosure without the rattlesnake.Results: The intramesencephalic non-specific blockade of opioid receptors with microinjections of naloxone at higher doses decreased both anxiety- (defensive attention and flat back approach) and panic attack-like (defensive immobility and escape) behaviors, evoked in the presence of rattlesnakes and increased non-defensive responses. During the exposure to the experimental context, there was a decrease in duration of defensive attention.Conclusions: These findings suggest a panicolytic-like effect of endogenous opioid receptors antagonism in the inferior colliculus on innate (panic attack) and conditioned (anticipatory anxiety) fear in rats threatened by rattlesnakes. [ABSTRACT FROM AUTHOR]