Experimental estrogen-induced hyperprolactinemia results in bone-related hearing loss in the guinea pig

Our group (Horner KC, Guieu R, Magnan J, Chays A, Cazals Y. Neuropsychopharmacology 26: 135–138, 2002) has earlier described hyperprolactinemia in some patients presenting inner ear dysfunction. However, in that study, it was not possible to determine whether hyperprolactinemia was a cause or an effect of the symptoms. To investigate the effect of hyperprolactinemia on inner ear function, we first developed a model of hyperprolactinemia in estrogen-primed Fischer 344 rats and then performed functional studies on pigmented guinea pigs. Hyperprolactinemia induced, after 2 mo, a hearing loss of ~30–40 dB across all frequencies, as indicated by the compound action potential audiogram. During the 3rd mo, the hearing loss continued to deteriorate. The threshold shifts were more substantial in males than in females. Observations under a dissection microscope revealed bone dysmorphology of the bulla and the cochlea. Light microscopy observations of cryostat sections confirmed bone-related pathology of the bony cochlear bulla and the cochlear wall and revealed morphopathology of the stria vascularis and spiral ligament. Scanning electron microscopy revealed loss of hair cells and stereocilia damage, in particular in the upper three cochlear turns and the two outermost hair cell rows. The data provide the first evidence of otic capsule and hair cell pathology associated with estrogen-induced prolonged hyperprolactinemia and suggest that conditions such as pregnancy, anti-psychotic drug treatment, aging, and/or stress might lead to similar ear dysfunction

Behavioral characterization of CD26 deficient mice in animal tests of anxiety and antidepressant-like activity.

CD26 exhibits a dipeptidylpeptidase-IV function (DPPIV) which regulates neuropeptide activity by N-terminal processing. Because abnormal plasma DPPIV was associated in mammals with behavioral changes, we examined the behavior of CD26-/- mice resulting from targeted inactivation of the gene. These animals had a decreased immobility in the forced swim and tail suspension tests, indicating a reduced depression-like behavior. We addressed some factors that could affect these results. No major differences between mutants and controls were observed in the black/white box test that investigates anxiety. In the hole-board apparatus that explores both curiosity and anxiety, CD26-/- mice of both genders made significantly more head dips than controls. In a motor activity test, mutants displayed higher horizontal and vertical activities i.e. increased novelty-induced behavioral activation. We conclude that DPPIV inactivation in mice broadly leads to an antidepressant-like and hyperactive phenotype

Involvement of endogenous opioid system in scorpion toxin-induced antinociception in mice.

International audienceThe present study analyzes the involvement of the endogenous opioid system in the antinociceptive effects produced in mammals after alpha- or beta- scorpion toxin injections. The analgesic effects on mice of the alpha-anatoxin Amm VIII, a weak modulator of Na(v)1.2 channel, and the depressant insect-selective beta-toxin LqqIT2 were evaluated by intraperitoneal route. The two toxins increased hot plate and tail flick latencies in a dose-dependent manner. We also compared the effects of the toxins with those obtained after acetic acid administration or cold-water tail immersion, which both induce pain relief through the activation of diffuse noxious inhibitory controls (DNIC) and the release of endogenous opioids. The increased latencies obtained with the toxins, acetic acid, or cold-water tail immersion were partly reversed by the co-administration of the opioid receptor antagonist naloxone. Finally, AmmVIII, LqqIT2, or acetic acid, induced increased c-fos mRNA expression in spinal cord. This increase disappeared when the toxins were co-injected with acetic acid. In conclusion, we show for the first time that an alpha-anatoxin exhibits a potent analgesic activity and confirm that depressant beta-toxins are able to reduce nociception. We hypothesize that pain relief induced by these scorpion toxins may implicate the activation of an endogenous opioid system and may be partly the result of a counter irritation phenomenon, which could be due to the activation of DNIC

Relationship between A2A adenosine receptor expression and intradialytic hypotension during hemodialysis.

BACKGROUND: Intradialytic hypotension (IDH) is a common complication of hemodialysis sessions (HDSs). Adenosine may contribute to the drop in blood pressure during IDH events because it has hypotensive effects. As A(2A) adenosine receptor expression is essential for blood pressure control, we compared the expression of A(2A) receptors (Bmax, K(D), and messenger ribonucleic acid [mRNA] levels) in peripheral blood mononuclear cells from IDH and non-IDH patients and from controls. We also evaluated adenosine plasma levels (APLs). METHODS: We included 10 hemodialyzed patients with at least three IDH events per month. We also included 11 hemodialyzed patients with no history of IDH events and 10 healthy subjects as controls. RESULTS: IDH patients had higher Bmax values than non-IDH patients (mean before HDS, +86%; after HDS, +112%), whereas non-IDH patients had lower Bmax values than controls (mean -72%). K(D) values were not significantly different between patients and controls. The levels of mRNA increased significantly during HDS but without an increase in receptor expression on the cell membranes. APLs were higher in hemodialyzed patients than in controls. CONCLUSION: We found that A(2A) receptors are more expressed in IDH patients than in non-IDH patients, whereas APL was high in all patients. Both high APL and a relative increase in A(2A) receptor expression may favor IDH events