Previous studies have shown significant changes in dopamine and opioid receptors in the basal ganglia following administration of cocaine. Cocaine administration results in a significant increase in the number of opioid receptors in dopamine-enriched brain regions. The aim of this study was to determine if dopamine D2 receptors (D2r) and -opioid receptors ( Or) are localized to the same neurons in the dorsolateral striatum. Immunoperoxidase and immunogold-silver labeling combined with electron microscopy was used to examine the ultrastructural localization of both receptors in the dorsolateral striatum. Approximately half of the Orlabeled somatodendritic processes showed immunolabeling for the D2r. Similarly, about half of the D2r-labeled dendrites and cell bodies showed immunolabeling for the Or. In conclusion, our results indicate that individual neurons in the rat dorsolateral striatum may be directly modulated by both dopaminergic and opioid ligands. These data also suggest that the molecular mechanism responsible for the up-regulation of Ors in the caudate and putamen following cocaine exposure may depend, in part, on the co-existence of D2rs and -Ors in these cells.
The objective of this study was to determine the effect of alendronate on the viability of canine osteosarcoma cells and nonneoplastic canine cells. The sample population was composed of canine osteosarcoma tumor cells. Osteosarcoma cells and canine fibroblasts were maintained in culture under standard conditions. The MTT assay for cell viability was performed after 24, 48, and 72 h of incubation with alendronate (0.001 to 1000 microM) or no drug (control). Plates were set up so that each concentration and the control had a sample number of 8. The optical density (OD) of each well was measured at 540 nm using an enzyme-linked immunosorbent assay microplate reader. The percent viability was determined for each concentration and for each incubation time. After 24 h of incubation of POS (parent osteosarcoma) and HMPOS cells with alendronate, there was no significant difference in mean OD at any drug concentration when compared with control samples. A significant concentration- and time-dependent reduction in mean OD of osteosarcoma cells was observed after 48 and 72 h of incubation, with alendronate concentrations ranging from 10 to 1000 microM. The lowest percent cell viability observed in treated cells was 35%. Conversely, alendronate did not significantly affect mean OD in fibroblasts, and the lowest percent cell viability observed was 76%. Our data indicate that alendronate may have the potential to inhibit canine osteosarcoma tumor growth. It will be important to determine the clinical relevance of these in vitro findings. If similar findings are observed in vivo, use of alendronate may also be indicated as an adjuvant to existing chemotherapeutic protocols.
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