Results Two of the naive middle-aged monkeys attained criterion performance, with weak stimulus Selleckchem MLN2238 control and few discrimination tests, despite
greater blood-ethanol concentration 60 min after 1.0 g/kg ethanol in middle-aged compared to young adult female monkeys (Green et al. in Alcohol Clin Exp Res 23: 611-616, 1999). The efficacy of the GABA(A) receptor positive modulators pentobarbital, midazolam, allopregnanolone, pregnanolone, and androsterone to substitute for the discriminative stimulus effects of 1.0 g/kg ethanol was maintained from young adulthood to middle age.
Conclusions The data suggest that 1.0 g/kg ethanol is a weak discriminative stimulus in naive middle-aged monkeys. Nevertheless, the GABA(A) receptor mechanisms mediating the discriminative stimulus effects of ethanol, when learned as a young adult, appear stable across one third of the primate lifespan.”
“Recent studies sight beta-adrenergic
receptor (AR) antagonists as novel therapeutic agents for melanoma, as they may reduce disease progression. Here within, we evaluated the expression of beta-ARs in a series of human cutaneous melanocytic lesions, and studied the effect of their endogenous agonists, norepinephrine Danusertib supplier (NE) and epinephrine (E), on primary and metastatic human melanoma cell lines. Using immunohistochemistry, we found that both beta 1- and beta 2-ARs are expressed in tissues from benign melanocytic naevi, atypical naevi and malignant melanomas and that expression
was significantly higher in malignant tumours. Melanoma cell lines (human A375 primary melanoma cell line and human Hs29-4T metastatic melanoma cell lines) also expressed beta 1- and beta 2-ARs by measuring transcripts and proteins. NE or E increased metalloprotease-dependent motility, released interleukin-6 and 8 (IL-6, IL-8) and vascular endothelial growth factor (VEGF). These effects of catecholamines were inhibited by the unselective beta-AR antagonist propranolol. The role of soluble factors elicited by catecholamines seemed pleiotropic as VEGF synergized with NE increased melanoma invasiveness VX-661 research buy through 3D barriers, while IL-6 participated in stromal fibroblast activation towards a myofibroblastic phenotype. Our results indicate that NE and E produce in vitro via beta-ARs activation a number of biological responses that may exert a pro-tumorigenic effect in melanoma cell lines. The observation that beta-ARs are upregulated in malignant melanoma tissues support the hypothesis that circulating catecholamines NE and E, by activating their receptors, favour melanoma progression in vivo. Laboratory Investigation (2013) 93, 279-290; doi:10.1038/labinvest.2012.175; published online 14 January 2013″
“Rationale Repeated treatment with morphine has been shown to sensitize rats to its stimulant effects on motor activity and mesolimbic dopamine (DA) transmission.