Dorsomedial hypothalamus serotonin 1A receptors mediate a panic-related response in the elevated T-maze.

The dorsomedial hypothalamus (DMH) has long been associated with the regulation of escape, a panic-related defensive response. Previous evidence has shown that the activation of serotonin (5-HT) 1A and 2A receptors impairs escape behavior induced by the electrical stimulation of the same region. In this study we further explore the relationship of the DMH with defense by investigating the effects of 5-HT1A activation on escape behavior generated in male Wistar rats by an ethologically based aversive stimuli, exposure to one of the open arms of the elevated T-maze (ETM).

5-HT1A and 5-HT2A receptor control of a panic-like defensive response in the rat dorsomedial hypothalamic nucleus.

The dorsomedial nucleus of the hypothalamus (DMH) has long been implicated in the genesis/regulation of escape, a panic-related defensive behavior. In the dorsal periaqueductal gray matter (dPAG), another key panic-associated area, serotonin, through the activation of 5-HT1A and 5-HT2A receptors, exerts an inhibitory role on escape expression. This panicolytic-like effect is facilitated by chronic treatment with clinically effective antipanic drugs such as fluoxetine and imipramine.

Serotonin-2A receptor regulation of panic-like behavior in the rat dorsal periaqueductal gray matter: the role of GABA.

Rationale: Electrical stimulation of the dorsal periaqueductal gray (dPAG) evokes escape, a defensive response associated with panic attacks. Stimulation of 5-HT1A or 5-HT2A receptors in this midbrain area equally inhibits escape performance, even though at the molecular level these receptors cause opposite effects, i.e.

5-HT2C receptor regulation of defensive responses in the rat dorsal periaqueductal gray.

Activation of 5-HT2C receptors in limbic structures such as the amygdala and hippocampus increases anxiety. Indirect evidence obtained with non-selective 5-HT2C-interacting drugs suggests that the same may occur in the dPAG, a brainstem region consistently implicated in the genesis/regulation of panic attacks. In this study we used more selective agonists and antagonists to unveil the role played by dPAG 5-HT2C receptors in the regulation of anxiety- and panic-related defensive behaviors.

Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors.

Activation of 5-HT1A receptors in the dorsal periaqueductal gray (dPAG) impairs escape behavior, suggesting a panicolytic-like effect. Cannabidiol (CBD), a major non-psychotomimetic compound present in Cannabis sativa, causes anxiolytic-like effects after intra-dPAG microinjections by activating 5-HT1A receptors. In the present work we tested the hypothesis that CBD could also impair escape responses evoked by two proposed animal models of panic: the elevated T-maze (ETM) and electric stimulation of dPAG.

Panicolytic-like effect of BDNF in the rat dorsal periaqueductal grey matter: the role of 5-HT and GABA.

A wealth of evidence suggests a role for brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) in the aetiology of depression and in the mode of action of antidepressant drugs. Less clear is the involvement of this neurotrophin in other stress-related pathologies such as anxiety disorders. The dorsal periaqueductal grey matter (DPAG), a midbrain area rich in BDNF and TrkB receptor mRNAs and proteins, has been considered a key structure in the pathophysiology of panic disorder.

Alprazolam potentiates the antiaversive effect induced by the activation of 5-HT(1A) and 5-HT (2A) receptors in the rat dorsal periaqueductal gray.

Rationale: Serotonin in the dorsal periaqueductal gray (DPAG) through the activation of 5-HT(1A) and 5-HT(2A) receptors inhibits escape, a defensive behavior associated with panic attacks. Long-term treatment with antipanic drugs that nonselectively or selectively blocks the reuptake of serotonin (e.g.

Cholecystokinin-2 receptors modulate freezing and escape behaviors evoked by the electrical stimulation of the rat dorsolateral periaqueductal gray.

Systemic injection of the cholecystokinin type 2 (CCK(2)) receptor agonist CCK-4 evokes panic attacks in humans and facilitates the expression of a panic-related defensive behavior, escape, in rats. Given the prominent role attributed to the dorsal periaqueductal gray (dPAG) in the pathophysiology of panic, this midbrain area has been assumed to be one of the key regions mediating these effects of CCK-4. However, only a few studies have directly investigated the role of dPAG CCK(2) receptors in the regulation of panic-related behaviors.

Effects of fluoxetine and buspirone on the panicolytic-like response induced by the activation of 5-HT1A and 5-HT2A receptors in the rat dorsal periaqueductal gray.

Rationale: Administration of 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptor agonists into the dorsal periaqueductal gray (DPAG) inhibits escape, a defensive behavior associated with panic attacks. Long-term treatment with the antipanic compound imipramine enhances the DPAG 5-HT1A- and 5-HT2A-receptor-mediated inhibition of escape, implicating these receptors in the mode of action of panicolytic drugs.

Objectives: In the present study, we investigated whether the inhibitory effect on escape elicited by the intra-DPAG injection of 5-HT1A and 5-HT2A receptor agonists is also enhanced after treatment with fluoxetine, another widely used antipanic drug.

Inhibitory avoidance memory retention in the elevated T-maze is impaired after perivascular manipulation of the common carotid arteries.

Perivascular manipulation promoted by the positioning of a silicone collar around the common carotid arteries causes local inflammation and has been suggested as an animal model of atherosclerosis. This manipulation induces biochemical and morphological changes that are similar to those observed in the early stage of atherosclerosis in humans. Based on evidences showing that atherosclerosis is associated with cognitive deficits in humans, we presently investigated the temporal consequences of the bilateral positioning of silicone collars around the common carotid arteries (n = 15) on inhibitory avoidance memory retention in male Wistar rats tested in the elevated T-maze.