Anti-panic effect of fluoxetine during late diestrus in female rats is mediated through GABAergic mechanisms in the dorsal periaqueductal gray.

Panic disorder is more frequent in women than in men. In women, vulnerability to panic is enhanced during the late luteal phase of the menstrual cycle. At this time secretion of progesterone and its neuroactive metabolite allopregnanolone (ALLO), which acts as a positive allosteric modulator of the actions of GABA at GABA receptors, decline sharply.

Neonatal limited bedding and nesting experience may lead to a sex-dependent increase in panic-like defensive behaviours in adult mice.

In humans, adverse physical and/or psychological traumas in childhood may predispose to developing psychiatric disorders in adulthood, including panic disorder. To model early life adversity in mice, we subjected male and female C57BL/6 J mice to a limited bedding and nesting (LBN) protocol between postnatal days 2-9 and investigated its effect on responsiveness to panicogenic challenges in adulthood. Panic-like escape behaviour was assessed during exposure to a high concentration of CO (20%) or in the beetle mania task (BMT), used to model respiratory and non-respiratory-related types of panic respectively.

Antinociceptive action of cannabidiol on thermal sensitivity and post-operative pain in male and female rats.

This study investigated the antinociceptive potential of cannabidiol (CBD) in male and female Wistar rats. The assessment and analysis included tail withdrawal to thermal stimulation (tail flick test) and mechanical allodynia induced by plantar incision injury (von Frey test). CBD reduced acute thermal sensitivity in uninjured animals and post-operative mechanical allodynia in males and females.

Sex and estrous cycle-linked differences in the effect of cannabidiol on panic-like responding in rats and mice.

Clinical and preclinical studies point towards anxiolytic actions of cannabidiol (CBD), but its effect in panic disorder has been less explored and few studies consider effects in females. We here compared the effect of CBD on the response of male and female rats and mice to a panicogenic challenge; exposure to low O (rats) or high CO (mice) paying attention in females to possible effects of estrous cycle phase. Male and female Sprague-Dawley rats and C57BL/6 J mice were exposed to 7% O for 5 min (rats) or 20% CO (mice) and escape behaviour, which has been associated with panic attacks, was quantified as undirected jumps towards the gas chamber's ceiling.

Sex-dependent differences in the anxiolytic-like effect of cannabidiol in the elevated plus-maze.

Rationale: Cannabidiol (CBD), the major non-psychoactive constituent of cannabis, has therapeutic potential for the treatment of anxiety. Most preclinical studies investigate only acute effects of CBD and only in males, yet the drug is most likely to be used over a sustained period in clinical practice.

Objectives: The objectives of this study were to investigate the anxiolytic-like effect of CBD in female rats compared to males and to determine whether the responsiveness of females was influenced by the stage of the estrous cycle.

Neonatal maternal deprivation facilitates the expression of a panic-like escape behavior in adult rats.

A wealth of evidence associates disruptions of the parent-infant relationship (e.g. childhood parental loss or parental neglect) with the later appearance of panic disorder.

Enhanced responsiveness to hypoxic panicogenic challenge in female rats in late diestrus is suppressed by short-term, low-dose fluoxetine: Involvement of the dorsal raphe nucleus and the dorsal periaqueductal gray.

Background: Acute hypoxia, which is panicogenic in humans, also evokes panic-like behavior in male rats. Panic disorder is more common in women and susceptibility increases during the premenstrual phase of the cycle.

Aims: We here investigated for the first time the impact of hypoxia on the expression of panic-like escape behavior by female rats and its relationship with the estrous cycle.

Panic-like responses of female Wistar rats confronted by Bothrops alternatus pit vipers, or exposure to acute hypoxia: Effect of oestrous cycle.

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% O ).

The Frequency-Dependence of Pre- and Postganglionic Nerve Stimulation of Pig and Rat Bladder.

Purpose: The urinary bladder generates phasic contractions via action potentials generated in pre- and then postganglionic neurons. Whilst the frequency-dependence of postganglionic neurons to generate contractions has been quantified, the dynamic range of preganglionic neurons is less clear and if intramural ganglia exert frequency-dependent modulation of transmission between pre- and postganglionic neurons. The phosphodiesterase type 5 inhibitor sildenafil reduces neurotransmitter release from postganglionic fibres to detrusor smooth muscle and an additional question was if there was also a preganglionic action.

Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety.

Anxiety disorders are more prevalent in women than in men. In women the menstrual cycle introduces another variable; indeed, some conditions e.g.

Acute and chronic cardiorespiratory consequences of focal intrahippocampal administration of seizure-inducing agents. Implications for SUDEP.

The risk factors for SUDEP are undoubtedly heterogenous but the main factor is the frequency of generalized tonic-clonic seizures with apnoea and/or cardiac abnormalities likely precipitating the lethal event. By its very nature modelling SUDEP experimentally is challenging, yet insights into the nature of the lethal event and precipitating factors are vital in order to understand and prevent fatalities. Acute animal models, which induce status epilepticus (SE), can be used to help understand pathophysiological processes during and following seizures, which sometimes lead to death.

Influence of estrous cycle stage on acquisition and expression of fear conditioning in female rats.

It is unclear whether all animal models of anxiety-like states developed using males are appropriate for use in females. In females, tests involving a learning component might be influenced not only by estrous cycle stage on the test day but also by the stage during the conditioning process. We used two tests - conditioned freezing (CF) and fear potentiated startle (FPS) to compare responsiveness of male rats and females conditioned and/or tested in proestrus (P) or late diestrus (LD).

Sacral nerve stimulation for refractory OAB and idiopathic urinary retention: Can phenotyping improve the outcome for patients: ICI-RS 2019?

Aims: Sacral nerve stimulation (SNS) is widely used to treat refractory idiopathic overactive bladder (OAB) and idiopathic urinary retention. However, clinical outcomes are variable and understanding predictive factors for success or side-effects would enable personalization of therapy and optimization of outcomes. At the International Consultation on Incontinence-Research Society meeting 2019, a Think Tank was convened to discuss how advances in the basic science study of SNS may be translatable into clinical practice to improve outcomes of patients undergoing SNS treatment.

Cardiac effects of repeated focal seizures in rats induced by intrahippocampal tetanus toxin: Bradyarrhythmias, tachycardias, and prolonged interictal QT interval.

Objective: To determine electrical changes in the heart in a chronic, nonstatus model of epilepsy.

Methods: Electrocorticography (ECoG) and electrocardiography (ECG) of nine animals (five made epileptic by intrahippocampal injection of tetanus neurotoxin (TeNT) and four controls), are monitored continuously by radiotelemetry for up to 7 weeks.

Results: Epileptic animals develop a median of 168 seizures, with postictal tachycardias reaching a mean of 487 beats/min and lasting a mean of 661 seconds.

Brainstem activity, apnea, and death during seizures induced by intrahippocampal kainic acid in anaesthetized rats.

Objective: To investigate how prolonged seizure activity affects cardiorespiratory function and activity of pre-Bötzinger complex, leading to sudden death.

Methods: Urethane-anesthetized female Long-Evans rats were implanted with nasal thermocouple; venous and arterial cannulae; and electrodes for electrocardiography (ECG) and hippocampal, cortical, and brainstem recording. Kainic acid injection into the ventral hippocampus induced status epilepticus.

Botulinum toxin A for refractory OAB and idiopathic urinary retention: Can phenotyping improve outcome for patients: ICI-RS 2019?

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.

Short-term, low-dose fluoxetine prevents oestrous cycle-linked increase in anxiety-like behaviour in female rats.

Background And Aims: We sought a robust behavioural test that evoked increased anxiety-like behaviour during the late dioestrus phase of the oestrous cycle (similar to the premenstrual period in women) and tested whether this could be prevented by acute low-dose fluoxetine (FLX).

Methods: Female Wistar rats in different stages of their cycle were exposed to four different tests of anxiety-like behaviour.

Results: No oestrous cycle differences were detected in fear potentiated startle or conditioned freezing to an aversive context.

Suppression of Urinary Voiding "on Demand" by High-Frequency Stimulation of the S1 Sacral Nerve Root in Anesthetized Rats.

Objectives: High-frequency (kHz) stimulation of preganglionic pelvic nerve afferents can inhibit voiding in both anesthetized and conscious rats. The afferents travel via the S1 sacral nerve root, which is easier to access than the distal pelvic nerve fibers within the abdominal cavity. We therefore investigated whether voiding could be inhibited by high-frequency stimulation at S1 and how this compared to distal pelvic nerve stimulation.

The endogenous opioid system modulates defensive behavior evoked by Crotalus durissus terrificus: Panicolytic-like effect of intracollicular non-selective opioid receptors blockade.

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).

Acid reflux induced laryngospasm as a potential mechanism of sudden death in epilepsy.

Objective: Recent research suggests that obstructive laryngospasm and consequent respiratory arrest may be a mechanism in sudden unexpected death in epilepsy. We sought to test a new hypothesis that this laryngospasm is caused by seizures driving reflux of stomach acid into the larynx, rather than spontaneous pathological activity in the recurrent laryngeal nerve.

Approach: We used an acute kainic acid model under urethane anesthesia to observe seizure activity in Long-Evans rats.

Suppression of Urinary Voiding by Conditional High Frequency Stimulation of the Pelvic Nerve in Conscious Rats.

Female Wistar rats were instrumented to record bladder pressure and to stimulate the left pelvic nerve. Repeated voids were induced by continuous infusion of saline into the bladder (11.2 ml/h) via a T-piece in the line to the bladder catheter.

Female psychopharmacology matters! Towards a sex-specific psychopharmacology.

There is increasing recognition that women have a higher prevalence of certain psychiatric illnesses, and a differential treatment response and course of illness compared to men. Additionally, clinicians deal with a number of disorders like premenstrual syndrome, premenstrual dysphoric disorder, and postpartum depression, which affect women specifically and for which treatment and biological pathways are still unclear. In this article we highlight recent research which suggests that different biological mechanisms may underlie sex differences in responsiveness to stress.

High Frequency Stimulation of the Pelvic Nerve Inhibits Urinary Voiding in Anesthetized Rats.

Urge Urinary Incontinence: "a sudden and uncontrollable desire to void which is impossible to defer" is extremely common and considered the most bothersome of lower urinary tract conditions. Current treatments rely on pharmacological, neuromodulatory, and neurotoxicological approaches to manage the disorder, by reducing the excitability of the bladder muscle. However, some patients remain refractory to treatment.