Evaluation of the effects of opioid agonists and antagonists under a delayed matching-to-sample procedure in pigeons

The effects of several opioid agonists and antagonists were examined in pigeons performing under a delayed matching-to-sample procedure. The mu agonists morphine and l-methadone, the kappa agonists U 50,488 and ethylketocyclazocine, and the opioid antagonist naloxone had no effect on the accuracy of responding. These drugs were, however, behaviorally active as evidenced by the dose-dependent decreases in rates of responding associated with their administration. In contrast, the sigma agonists (+) N-allylnormetazocine and phencyclidine decreased the accuracy of responding in a dose-dependent fashion. The relative magnitude of these drug-induced decreases in accuracy were similar across the no delay (0-s), short (2-s), and long (8-s) delay intervals. For these drugs, accuracy-decreasing effects were obtained only at doses that reduced rates of responding. The results of the present investigation parallel those reported in pigeons responding under drug discrimination tasks, in which the discriminative stimulus properties produced by the mu and kappa agonists are similar to each other but distinguishable from those produced by the sigma agonists.Recipient of Research Scientist Development Award DA 00033 from the National Institute on Drug Abuse     

Transplant data: sources, collection and research considerations, 2004

The process of collecting and analyzing transplant data is complex. Familiarity with how these data are collected is crucial to a thorough understanding of the information. This article focuses on available OPTN-SRTR data and the continuing evolution of data collection mechanisms; how that data collection system is improving the data quality and reducing the data collection burden; how additional ascertainment of outcomes both completes and validates existing data; and caveats that remain for researchers. This year's article focuses further on research considerations related to cohort choice, timing of data submission, and potential biases in follow-up data. Ongoing improvements in data collection timeliness and scope are covered. The impact of extra ascertainment of outcomes, particularly for post-transplant kidney graft failure from Medicare data, are also examined. A section on graft failure reporting among different sources traces the steps by which the SRTR reconciles different data sources in its analyses. It is important that those reading and conducting transplant research understand the origin, structure, and scope of the available data. All of these issues should be carefully considered when choosing cohorts and data sources for analysis.     

Some behavioral effects of repeated d-amphetamine administrations

Effects of daily administrations of d-amphetamine were studied on key peck responses of pigeons maintained under a multiple fixed-interval 2-min, fixed-ratio 30-responseschedule. Under the fixed-interval schedule, a pause was followed by a transition to increasing rates of responding until food presentation. Under the fixed-ratio schedule, higher sustained rates of responding were maintained. Low to intermediate doses (0.3-1.0 mg/kg) of d-amphetamine changed the temporal patterns and occasionally increased rates of responding under the fixed-interval schedule. Higher doses decreased rates of responding under bothschedules. With daily injections of 1.0 mg/kg d-amphetamine prior to experimental sessions, the effects of this dose on rates and patterns of responding were attenuated, and d-anphetamine dose-effect curves were shifted to the right, primarily under the fixed-ratio schedule. Similar results were obtained with daily presession injections of 5.6 mg/kg d-amphetamine in a second group of pigeons, except that rates of responding under both schedules were decreased by this daily dose, and did not return completely to control values with repeated injections. In a third group of pigeons, 1.0 mg/kg d-amphetamine administered daily, after experimental sessions, did not alter dose-effect functions for d-amphetamine. In a second experiment, pigeons were trained to peck one response key when given 1.0 mg/kg d-amphetamine and a different key when given presession water injections. Increasing doses of d-amphetamine produced incresing percentages of d-amphetamine-key responses. Repeated administration of 5.6 mg/kg d-amphetamine shifted these dose-effect functions to the right one-half log unit. Results suggested that decreases in reinforcement frequency are not a necessary condition for the development of behavioral tolerance to d-amphetamine.     

Epstein-Barr virus coopts lipid rafts to block the signaling and antigen transport functions of the BCR

The B cell antigen receptor (BCR) functions to initiate signaling and to internalize antigen for processing from within Lyn kinase-enriched membrane lipid rafts. The signaling function of the BCR is blocked by Epstein-Barr Virus (EBV) latent membrane protein 2A (LMP2A), which is constitutively phosphorylated by Lyn. Here, we show that LMP2A resides in lipid rafts and excludes the BCR from entering rafts by Lyndependent mechanisms, thus blocking both BCR signaling and antigen transport. Mutant LMP2A that permits BCR signaling and raft translocation still blocks antigen trafficking, indicating independent control of these BCR functions. Thus, EBV coopts the lipid rafts to disarm both the signaling and antigen-processing functions of the BCR by independent mechanisms.     

Scedosporium inflatum, an emerging pathogen.

The salient morphologic and physiologic characteristics of 18 isolates of Scedosporium inflatum, a newly reported human pathogen, were compared with those of the morphologically similar fungi Scedosporium apiospermum, Scopulariopsis brevicaulis, and Scopulariopsis brumptii. The formation by S. inflatum of annelloconidia in wet clumps at the apices of annellides with swollen bases was found to be the most useful characteristic in differentiating this potential pathogen.     

Management of rectal injuries. Dogma versus practice

The current treatment of civilian rectal injuries stems from military practice. Five principles have evolved: 1) complete fecal diversion, 2) debridement and closure, 3) rectal stump irrigation, 4) presacral drainage, and 5) broad spectrum antibiotics. To assess our practice results, the records of 52 consecutive patients with rectal injury seen at Detroit Receiving Hospital from 1980-88 were reviewed. Etiologies were gunshot (40), shotgun (9), anal assault (2), and stab (1). There were no blunt injuries and no deaths. Treatment consisted of celiotomy (52), diverting colostomy (51), presacral drains (35), rectal stump irrigation (26), and primary closure (1). Broad spectrum antibiotics were administered in all patients. Despite lack of universal application of the "standard" principles, only five patients had postoperative complications and none were related to the rectal injury. Our results demonstrate that a single approach may not be justified, as excellent outcome was achieved with low morbidity and no mortality despite selective management. The universal application of colostomy, repair, irrigation, drainage, and antibiotics cannot be supported.     

Serotonin involvement in the discriminative stimulus effects of mu and kappa opioids in rats

The role of serotonin (5-HT) in the discriminative stimulus effects of opioids was examined using a two-lever, food-reinforced drug discrimination procedure. The effects of the 5-HT(1A) full agonist 8-OH-DPAT, the 5-HT(1A) partial agonist buspirone and the 5-HT(2) antagonist ketanserin were evaluated in rats trained to discriminate the mu opioid agonist morphine, or the kappa opioid agonist U50, 488 from saline. In rats trained to discriminate 5.6mg/kg of morphine from saline, morphine dose-dependently substituted (produced >/= 80% morphine-appropriate responding) for the morphine stimulus. In contrast, U50,488, 8-OH-DPAT and ketanserin did not substitute for morphine, and buspirone produced only a small degree of substitution (approx. 40% morphine-appropriate responding). When administered in combination with morphine, 8-OH-DPAT, but not buspirone and ketanserin, attenuated the discriminative stimulus effects of higher doses of morphine. In rats trained to discriminate 5.6mg/kg of U50, 488 from saline, U50, 488 dose-dependently substituted for the U50, 488 stimulus. When administered alone, 8-OH-DPAT and buspirone partially substituted (produced between 40% and 79% U50, 488-appropriate responding) for the U50,488 stimulus, whereas morphine and ketanserin did not substitute for U50,488. The opioid antagonist naltrexone failed to antagonize the effects of 8-OH-DPAT and buspirone suggesting that the effects of these drugs in U50,488-trained rats were not mediated by opioid receptors. When administered in combination with U50,488, 8-OH-DPAT, but not buspirone or ketanserin, attenuated the discriminative stimulus effects of the training dose of U50,488. These results suggest that the 5-HT system is involved in the discriminative stimulus effects of both morphine and U50,488, although the exact nature of this 5-HT involvement is not clear.