An analysis of the paradoxical effect of morphine on runway speed and food consumption

A previously reported paradigm in which rats run down a runway for food reward followed by morphine injection was analyzed to assess the utility of the paradigm in studies of opiate reinforcement. One experiment replicated the original report that post-trial morphine caused both an increase in runway speed and a decrease in food consumption (taste aversion) over successive trials, and showed in addition that the increase in runway speed did not occur as a result of food deprivation alone, but required the animals to have consumed food in the goal box. A second study using the quaternary opiate antagonist methyl naltrexone to block the peripheral effects of morphine suggested that the increase in runway speed has a peripheral locus while the taste aversion has a central one. A third experiment in which morphine was microinjected into either the lateral ventricle or the ventral tegmental area supported these observations, in that intracranial morphine failed to result in an increased runway speed, but did produce taste aversion after microinjection into either site. These findings also suggest that the increase in runway speed caused by post-trial morphine in this experiment has a peripheral locus of effect, which is probably distinct from the central effect that supports morphine self-administration and conditioned place preference. Offprint requests to: W.A.CorrigallThe views expressed in this publication are those of the authors and do not necessarily reflect those of the Addiction Research Foundation     

The surgical risk of colectomy in patients with cirrhosis

The records of 54 patients with documented cirrhosis who underwent colectomy between January 1970 and January 1984 were studied to assess the operative risk and to determine the preoperative predictive risk factors. In-hospital mortality was 24 percent (13 patients), and postoperative complications occurred in 48 percent (26 patients). The risk of surgical intervention was significantly increased if encephalopathy, ascites, anemia, or hypoalbuminemia was present before operation. A simple operative risk index involving the presence of encephalopathy and ascites and the levels of hemoglobin and albumin is proposed to help distinguish a low-risk subgroup in whom postoperative mortality was 12.8 percent from a high-risk subgroup in whom postoperative mortality was 53.3 percent.     

Effect of 2 ppm ozone exposure on rat lung lipid fatty acids

Based on in vitro studies, the initial damage to lung cells by ozone exposure is believed to result in part from the breakdown of lipid polyunsaturated fatty acids to aldehydes, ozonides, and peroxides. The present study measured lipid breakdown products in lungs isolated from rats pretreated with [1-14C]acetate 12 h before exposure for 4 h to either air or 2 ppm ozone. Lipid fatty acid breakdown was indicated by a 112% increase in thiobarbituric acid-reactive substances on ozone exposure and by changes in chemical and radioactive measurements of mono- and dicarboxylic acids formed by treatment of lipid fractions with hydrogen peroxide. Ozone exposure resulted in a 63% increase in recovery of short-chain fatty acids accounted for by increased recoveries of malonic acid by 37%, hexanoic acid by 47%, nonanoic acid by 118%, and azelaic acid by 107%. Recovery of glutaric acid was enhanced 15-fold by ozone exposure. Although decreases in tissue arachidonic acid could not be detected, oleic acid was significantly decreased by 36%. Recovery of radiolabel as short-chain fatty acids was increased by 65% on ozone exposure and was mainly accounted for by enhanced labeling of nonanoic and glutaric acid fractions. The failure to observe significant increases in 14C recovery in the other fractions suggested ozone-induced breakdown of unlabeled fatty acids. These results demonstrate the cleavage of unsaturated fatty acid double bonds following in vivo exposure of lungs to ozone. Breakdown of arachidonic and oleic acids was specifically identified by increased recoveries of glutaric and nonanoic acids, respectively.     

Detection of Bacteroides fragilis Enterotoxin Gene by PCR

Bacteroides fragilis constitutes about 1% of the bacterial flora in intestines of normal humans. Enterotoxigenic strains of B. fragilis have been associated with diarrheal diseases in humans and animals. The enterotoxin produced by these isolates induces fluid changes in ligated intestinal loops and an in vitro cytotoxic response in HT-29 cells. We developed a nested PCR to detect the enterotoxin gene of B. fragilis in stool specimens. After DNA extraction, a 367-bp fragment was amplified with two outer primers. The amplicon from this reaction was subjected to a second round of amplification with a set of internal primers. With these inner primers, a 290-bp DNA fragment was obtained which was confirmed as part of the B. fragilis enterotoxin gene by Southern blotting with a nonradioactive internal probe and a chemiluminescence system. By this approach, B. fragilis enterotoxin gene sequences were detected in eight known enterotoxigenic human isolates and nine enterotoxigenic horse isolates. No amplification products were obtained from DNA extracted from 28 nonenterotoxigenic B. fragilis isolates or B. distasonis, B. thetaiotaomicron, B. uniformis, B. ovatus, Escherichia coli, or Clostridium difficile. The sensitivity of this assay allowed us to detect as little as 1 pg of enterotoxin DNA sequences or 100 to 1,000 cells of enterotoxigenic B. fragilis/g of stool. Enterotoxin production of all isolates was confirmed in vitro in HT-29 cells. A 100% correlation was obtained between enterotoxin detection by cytotoxin assay and the nested PCR assay. This rapid and sensitive assay can be used to identify enterotoxigenic B. fragilis and may be used clinically to determine the role of B. fragilis in diarrheal diseases.     

Nociceptin (Orphanin FQ) abolishes gestational and ovarian sex steroid-induced antinociception and induces hyperalgesia

Nociceptin (Orphanin FQ) is a newly discovered endogenous heptadecapeptide substrate for the opioid-receptor-like 1 receptor, a G protein coupled receptor that bears striking amino acid sequence homology to opiate receptors. In rats, intrathecal (i.t.) administration of nociceptin is without effect on basal thresholds for responsiveness to electric foot shock. However, during either late gestation or its hormonal simulation, when nociceptive thresholds are elevated by approximately 70%, i.t. nociceptin substantially attenuates jump thresholds in a dose-dependent fashion. This hypoalgesic effect of nociceptin is not limited to attenuating the gestational or sex steroid-induced increment in pain thresholds. Following the highest i.t. dose of nociceptin employed (20 nmol), the gestational or sex steroid-induced increment in jump thresholds is not only abolished but a significant hyperalgesia is observed. These results underscore the importance of the hormonal milieu to nociceptin hypoalgesic sensitivity. The potential contribution of spinal nociceptive pathways that utilize nociceptin to the etiology of extraordinary painful pregnancy and labor should not be ignored.     

Total cortisol,free cortisol,and growth hormone associated with brief social separation experiences in young macaques

Many behavioral, immunological, and physiological consequences of brief maternal separation in bonnet (Macaca radiata) and pigtail monkeys (Macaca nemistrina) have been documented. However, the impact of social separation on plasma cortisol and growth hormone is unknown for these particular species. In the present study, the behavioral and endocrinological consequences of a 2-week maternal separation in socially housed infant bonnet and pigtail monkeys were followed. In seven pairs (separated and matched control) of bonnet and six pairs of pigtail infants, plasma was obtained under baseline, separated, and reunion conditions twice weekly for the duration of the study. Blood samples were obtained from both infants of the pair in approximately 10 min. Plasma total cortisol, free cortisol, and growth hormone were measured in these samples. Focal animal behavioral observations were made on all subjects twice daily throughout the study period. In both species, total cortisol and free cortisol rose immediately following maternal separation in comparison to the matched nonseparated controls and returned to basal levels (e.g., that of matched non-separted controls) following reunion with the mother. In contrast, plasma growth hormone rose only in the pigtail infants over a time course that peaked around the time of reunion. Multiple regression techniques indicated for the first week of separation, in the separated but not control subjects, that mean plasma free and total cortisol was positively related to distress behaviors (vocalization and postural slouch) observed during this week and negatively related to social behaviors (play and proximity to others) noted during the same period. In contrast, plasma growth hormone was related to both species and sex of the subjects but unrelated to behavioral variables. © 1995 John Wiley & Sons, Inc.