Ionic currents influencing spontaneous firing and pacemaker frequency in dopamine neurons of the ventrolateral periaqueductal gray and dorsal raphe nucleus (vlPAG/DRN): A voltage-clamp and computational modelling study

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. We also evaluated functional activation of the midbrain panic circuitry in response to this panicogenic stimulus and whether short-term, low-dose fluoxetine treatment inhibits the hyper-responsiveness of females in late diestrus. Methods: Male and female Sprague Dawley rats were exposed to 7% O2. Females in late diestrus were also tested after short-term treatment with fluoxetine (1.75 or 10 mg/kg, i.p.). Brains were harvested and processed for c-Fos and tryptophan hydroxylase immunoreactivity in the periaqueductal gray matter (PAG) and dorsal raphe nucleus (DR). Results: Acute hypoxia evoked escape in both sexes. Overall, females were more responsive than males and this is clearer in late diestrus phase. In both sexes, hypoxia induced functional activation (c-Fos expression) in non-serotonergic cells in the lateral wings of the DR and dorsomedial PAG, which was greater in late diestrus than proestrus (lowest behavioral response to hypoxia). Increased responding in late diestrus (behavioral and cellular levels) was prevented by 1.75, but not 10 mg/kg fluoxetine. Discussion: The response of female rats to acute hypoxia models panic behavior in women. Low-dose fluoxetine administered in the premenstrual phase deserves further attention for management of panic disorders in women.

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Effects of Electroacupuncture of Different Frequencies on the Release Profile of Endogenous Opioid Peptides in the Central Nerve System of Goats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/476457 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 18

Author(s):

Li-Li Cheng ◽

Ming-Xing Ding ◽

Cheng Xiong ◽

Min-Yan Zhou ◽

Zheng-Ying Qiu ◽

...

Keyword(s):

Nucleus Accumbens ◽

Pain Threshold ◽

Dorsal Raphe Nucleus ◽

Periaqueductal Gray ◽

Locus Ceruleus ◽

Release Profile ◽

Raphe Nucleus ◽

Septal Area ◽

Dynorphin A ◽

Dorsal Raphé

To investigate the release profile of met-enkephalin,β-endorphin, and dynorphin-A in ruminants’ CNS, goats were stimulated by electroacupuncture of 0, 2, 40, 60, 80, or 100 Hz for 30 min. The pain threshold was measured using potassium iontophoresis. The peptide levels were determined with SABC immunohistochemisty. The results showed that 60 Hz increased pain threshold by 91%; its increasing rate was higher (P<0.01) than any other frequency did. 2 Hz and 100 Hz increased met-enkephalin immunoactivities (P<0.05) in nucleus accumbens, septal area, caudate nucleus, amygdala, paraventricular nucleus of hypothalamus, periaqueductal gray, dorsal raphe nucleus, and locus ceruleus. The two frequencies elicitedβ-endorphin release (P<0.05) in nucleus accumbens, septal area, supraoptic nucleus, ventromedial nucleus of hypothalamus, periaqueductal gray, dorsal raphe nucleus, locus ceruleus, solitary nucleus and amygdala. 60 Hz increased (P<0.05) met-enkephalin orβ-endorphin immunoactivities in the nuclei and areas mentioned above, and habenular nucleus, substantia nigra, parabrachial nucleus, and nucleus raphe magnus. High frequencies increased dynorphin-A release (P<0.05) in spinal cord dorsal horn and most analgesia-related nuclei. It suggested that 60 Hz induced the simultaneous release of the three peptides in extensive analgesia-related nuclei and areas of the CNS, which may be contributive to optimal analgesic effects and species variation.

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