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“Rationale While the N-methyl-D-aspartate (NMDA) glutamate receptor has been strongly implicated in chronic opiate dependence, relatively few studies have examined the effects of NMDA receptor antagonists on withdrawal from acute opiate exposure.

Objectives The current study examined the effects of memantine, a well-tolerated NMDA receptor antagonist, on acute opiate dependence as assessed by elevations in rodent startle responding (i.e., “”withdrawal-potentiated startle”") and increased pain sensitivity (i.e., hyperalgesia).

Results Administration of memantine either attenuated (5 mg/kg) or blocked (10 mg/kg) the

expression of withdrawal-potentiated startle during naloxone (2.5 mg/kg)-precipitated withdrawal eFT-508 from a single dose of morphine sulfate (10 mg/kg). Pre-treatment with the NMDA Evofosfamide receptor antagonist also inhibited the exacerbation of withdrawal-potentiated startle across

repeated acute opiate exposures. Memantine blocked the expression of acute dependence, but was less effective in inhibiting its escalation, when hyperalgesia was used as a measure of withdrawal. These doses of memantine did not affect startle responding or nociception in otherwise drug-free animals. Data from additional control groups indicated that the effects of memantine on the expression of withdrawal were not influenced by nonspecific interactions between the NMDA antagonist and either morphine or naloxone.

Conclusions These findings suggest that the see more NMDA receptor may play a key role in the earliest stages of opiate dependence and provide further evidence that memantine may be useful for the treatment of opiate withdrawal.”
“Coat protein complex II (COPII) is a multi-subunit

protein complex responsible for the formation of membrane vesicles at the endoplasmic reticulum. The assembly of this complex on the endoplasmic reticulum membrane needs to be tightly regulated to ensure efficient and specific incorporation of cargo proteins into nascent vesicles. Recent studies of a genetic disease affecting CON function, and a structural analysis of COPII subunit interactions emphasize the central role of the Sec23 subunit in COPII coat assembly. Similarly, the demonstration that Sec23 interacts physically and functionally with proteins involved in both vesicle tethering and the transport along microtubules indicates that the Sec23 subunit is crucially important in linking CON vesicle formation to anterograde transport events.”
“Oncolytic herpes simplex virus 1 (HSV-1) viruses armed with immunomodulatory transgenes have shown potential for enhanced antitumor therapy by overcoming tumor-based immune suppression and promoting antitumor effector cell development.