ABSTRACT
Compared to DBA/2J (D2), C57BL/6J (B6) inbred mice exhibit strong morphine preference when tested using a two-bottle choice drinking paradigm. A morphine preference quantitative trait locus (QTL), Mop2, was originally mapped to proximal chromosome (Chr) 10 using a B6xD2 F2 intercross population, confirmed with reciprocal congenic strains and fine mapped with recombinant congenic strains. These efforts identified a â¼ 10-Million base pair (Mbp) interval, underlying Mop2, containing 35 genes. To further reduce the interval, mice from the D2.B6-Mop2-P1 congenic strain were backcrossed to parental D2 mice and two new recombinant strains of interest were generated: D2.B6-Mop2-P1.pD.dB and D2.B6-Mop2-P1.pD.dD. Results obtained from testing these strains in the two-bottle choice drinking paradigm suggest that the gene(s) responsible for the Mop2 QTL is one or more of 22 remaining within the newly defined interval (â¼ 7.6 Mbp) which includes Oprm1 and several other genes related to opioid pharmacology. Real-time qRT-PCR analysis of Oprm1 and opioid-related genes Rgs17, Ppp1r14c, Vip, and Iyd revealed both between-strain and within-strain expression differences in comparisons of saline- and morphine-treated B6 and D2 mice. Analysis of Rgs17 protein levels also revealed both between-strain and within-strain differences in comparisons of saline- and morphine-treated B6 and D2 mice. Results suggest that the Mop2 QTL represents the combined influence of multiple genetic variants on morphine preference in these two strains. Relative contributions of each variant remain to be determined.
Subject(s)
Drug-Seeking Behavior/physiology , Morphine/administration & dosage , Narcotics/administration & dosage , Quantitative Trait Loci , Analgesics, Non-Narcotic/administration & dosage , Animals , Brain/physiology , Choice Behavior/drug effects , Choice Behavior/physiology , Drinking Behavior/drug effects , Drinking Behavior/physiology , Gene Expression/physiology , Mice, Inbred C57BL , Mice, Inbred DBA , Quinine/administration & dosage , RGS Proteins/metabolism , Species SpecificityABSTRACT
BACKGROUND: The aim of this study was to determine the predictive risk factors for complications resulting from foreign body ingestion. METHODS: A consecutive series of 1338 patients with suspected foreign body ingestion presenting from 1996 to 2000 were studied retrospectively. The potential risk factors for complications after foreign body ingestion were analysed by multivariate logistic regression and included concurrent medical illness, age, duration and types of symptoms, types of foreign body ingested, positive cervical radiographic findings and the level of foreign body impaction. RESULTS: Fish bone (62.7 per cent) was the commonest type of foreign body ingested. Most of the objects were impacted at or above the cricopharyngeus, the commonest site being the valleculae (31.4 per cent). Multivariate analysis showed that presentation delayed for more than 2 days (P < 0.001), positive cervical radiographic findings (P < 0.001) and foreign body impacted at the cricopharyngeus (P = 0.009) or upper oesophagus (P = 0.005) were significant independent risk factors associated with the development of complications after foreign body ingestion. CONCLUSION: In patients with a foreign body seen on plain cervical radiography, presentation delayed for more than 2 days after ingestion, and foreign body impacted at the level of the cricopharyngeus or oesophagus there is a high degree of correlation with the occurrence of complications. Awareness should be raised when these risk factors are present.
