Results demonstrate that intracerebral ventricular administration of CXCL12 (25 ng/4 mu l) 15 min prior to cocaine (20 mg/kg intraperitoneal (i.p.)) produced a significant potentiation of both ambulatory and stereotypic activity as compared to cocaine alone. The effects of CXCL12 were blocked by administration of the selective CXCR4 antagonist, AMD 3100. Administration of CXCL12 into specific brain regions was performed to further understand the site of action of CXCL12. Bilateral administration NU7441 solubility dmso of CXCL12 (25 ng/0.5
mu l) into the ventral tegmental area 15 min prior to cocaine (20 mg/kg i.p.) significantly potentiated cocaine-induced ambulatory activity, whereas microinjections of CXCL12 into the cauclate putamen selectively increased stereotypy. Conversely, administration of CXCL12 into the lateral shell of the nucleus accumbens resulted in an inhibition of cocaine-stimulated ambulatory activity. No alterations in ambulatory or stereotypic activity were observed following CXCL12 administration into the core of the nucleus accumbens. These results demonstrate that CXCL12 can modulate the behavioral effects produced by cocaine in a brain regionspecific manner. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Fas-associated protein with death domain (FADD) is a multifunctional
protein that can induce both apoptotic and non-apoptotic actions. Recently, FADD was found down-regulated in check details the prefrontal cortex of opiate abusers, which suggested an attenuation of Fas death signals
in human addicts. Phosphorylation of FADD (Ser194) has been reported to regulate its non-apoptotic activity, which might include the induction of neuroplastic effects in the brain. This postmortem brain study examined the status of phosphorylated (p)-Ser194 FADD and signaling pathways involved in neuroplasticity in the prefrontal cortex (BA 9) of short-term (ST) and long-term (LT) heroin or methadone abusers. In these subjects, the content of monomeric p-FADD was significantly increased when compared with that in age-, Rapamycin order gender-, and postmortem delay-matched controls (all addicts: 65%, n=26; ST abuse: 51%; n=11; LT abuse: 75%, n=15). Oligomeric p-FADD forms were modestly increased (11%-23%). At the subcellular level, opiate addiction upregulated the expression of monomeric p-FADD in the nucleus (110%) and that of p-oligomers in the cytosol (66%). In LT opiate addicts (but not ST abusers), a pronounced downregulation of p-extracellular signal-regulated kinase (ERK)1/2 (52%) and p-c-Jun NH2-terminal protein kinase (JNK)1/2 (51%), but not p-p38 mitogen-activated protein kinase (MAPK), was quantified in the prefrontal cortex (total homogenate and subcellular compartments).