98 research outputs found
Profiling the effects of repetitive morphine administration on motor behavior in rats
Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereasanalgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levelsof analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing onnon-analgesic effects has been overlooked. This study aimed to characterize morphine-inducedbehavior and the development and progression of morphine-induced behavioral tolerance. Adultmale Sprague–Dawley rats were repetitively treated with subcutaneous morphine for 14 days in twodose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day).Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in anopen-field arena, before and 30 min post-injections. Antinociception was measured using tail-flickand hot-plate assays. All measured parameters were highly suppressed in both dosing groups onthe first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatmentprogressed. Animals in the high-dose group showed increased locomotor activity after 10 days ofmorphine treatment. This excitatory phase converted to an inhibition of behavior when a highermorphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive highdose morphine exposure represent a signature of its behavioral and antinociceptive tolerance
Spectrum of Eleven-dimensional Supergravity on a PP-wave Background
We calculate the spectrum of the linearized supergravity around the maximally
supersymmetric pp-wave background in eleven dimensions. The resulting spectrum
agrees with that of zero-mode Hamiltonian of a supermembrane theory on the
pp-wave background. We also discuss the connection with the Kaluza-Klein zero
modes of AdS_4 x S^7 background.Comment: 17 pages, no figures, LaTeX2e, typos correcte
Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage.
A defective response to DNA damage is observed in several human autosomal
recessive ataxias with oculomotor apraxia, including ataxia-telangiectasia. We
report that senataxin, defective in ataxia oculomotor apraxia (AOA) type 2, is a
nuclear protein involved in the DNA damage response. AOA2 cells are sensitive to
H2O2, camptothecin, and mitomycin C, but not to ionizing radiation, and
sensitivity was rescued with full-length SETX cDNA. AOA2 cells exhibited
constitutive oxidative DNA damage and enhanced chromosomal instability in
response to H2O2. Rejoining of H2O2-induced DNA double-strand breaks (DSBs) was
significantly reduced in AOA2 cells compared to controls, and there was no
evidence for a defect in DNA single-strand break repair. This defect in DSB
repair was corrected by full-length SETX cDNA. These results provide evidence
that an additional member of the autosomal recessive AOA is also characterized by
a defective response to DNA damage, which may contribute to the neurodegeneration
seen in this syndrome
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