The Cerebral Cortex of the Rat and Visual Attentional Function: Dissociable Effects of Mediofrontal, Cingulate, Anterior Dorsolateral, and Parietal Cortex Lesions on a Five-Choice Serial Reaction Time Task

Dissociable effects of bilateral excitotoxic lesions of differentregions of the rat neocortex, including medial prefrontal andanterior cingulate cortices, were investigated in a five-choiceserial reaction time task that provides several indices of theaccuracy and speed of attentional function. Whereas medial prefrontalcortical lesions impaired performance of the task as revealedby a reduction in choice accuracy, an increase in the latencyto respond correctly to the visual target and enhanced perseverativeresponding, lesions of the anterior cingulate cortex specificallyincreased premature responding. By contrast, lateral frontalcortical lesions did not significantly disrupt baseline performanceof the task, but rather increased the latency to respond correctlyto the visual target during various behavioral manipulations,for example, when the length of the intertrial interval wasvaried unpredictably and during interpolation of distractingbursts of white noise. Lesions of the parietal cortex failedto disrupt any aspect of task performance investigated. These behavioral effects in the five-choice task were comparedwith the effect of these same lesions on acquisition and retentionof a one-trial passive avoidance task. The main finding fromthis paradigm was that lesions of the lateral frontal cortexproduced a significant disruption to the retention of passiveavoidance, which stands in marked contrast to the successfulretention observed by animals of the other lesion groups. Inaddition, this pattern of results reveals that the "disinhibitory"effect of cingulate cortex lesions are relatively specific tothe five-choice attentional task. Finally, the results of the present study are compared withthe findings of previous experiments using the five-choice task,which have examined the effect of selective manipulations ofthe ascending noradrenergic, cholinergic, dopaminergic. andserotonergic projections. In particular, the deficits in attentionalfunction observed following cholinergic lesions of the nucleusbasalis magnocellularis appear to be attributable to cholinergicdenervation of the medial frontal cortex. These results arediscussed in terms of the role of parallel distributed neuralsystems within the neocortex that mediate continuous attentionalperformance in the rat.     

Suits happen

Does your agency have enough malpractice insurance to protect you if you're involved in a lawsuit? Many EMTs are taking matters into their own hands.     

T-maze learning, spontaneous activity and food intake recovery following systemic administration of the noradrenaline neurotoxin, DSP4

Following systemic administration of the noradrenaline (NA) neurotoxin, DSP4 (50 mg/kg), rats were found to be retarded in the rate at which they acquired the "right-turn" running response in a modified T-maze choice situation, as measured by the total number of errors per session and median latency to reach the goal box. Desipramine (DMI, 20 mg/kg), injected 30 min before DSP4 blocked the acquisition retardation. DSP4 was found to have a short-lasting effect upon spontaneous motor activity, while food and water intake recovery was complete within 7 days of the injection. Both the NA-accumulation data and endogenous NA concentrations indicated profound NA, but not 5-hydroxytryptamine (5-HT) and dopamine (DA), depletions in the cortex, hippocampus and cerebellum. These data seem to confirm the role of the locus coeruleus-noradrenaline (LC-NA) system in an instrumental learning situation.     

A plasma factor enhances activity of vitamin K-dependent coagulation proteins

A plasma factor, "coagulopoietin", present in animals with depleted vitamin K-dependent coagulation factors, appears to enhance activity of these factors in normal animals. We have investigated the effects of "coagulopoietin" on synthesis of certain coagulation proteins by the isolated rat liver perfused for eight hours. Liver donor rats received plasma injections from vitamin K-deficient rats or from normal rats 24 hr before sacrifice. Coagulation activity of Factor VII and Factor II in liver perfusate samples was measured with a coagulation assay; Factor II synthesis was also measured by rocket immunoelectrophoresis and by activation with E. carinatus venom. Cumulative hepatic synthesis of Factor VII coagulation activity was increased by 43% when rat liver donors received vitamin K-deficient rat plasma compared to normal rat plasma. Cumulative synthesis of Factor II coagulation activity was increased by 51%, but synthesis of the protein measured immunologically or by activation with venom was not affected. The "coagulopoietin" factor in these studies appears to increase measurable coagulation factor activity without increasing total protein synthesis.     

Pharmacokinetics and pharmacodynamics of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione in patients with postmenopausal breast cancer

Summary The pyridylglutarimide 3-ethyl-3-(4-pyridyl)-piperidine-2,6-dione (PyG) is a novel inhibitor of aromatase that was shown to cause effective suppression of plasma oestradiol levels in postmenopausal patients. In four patients receiving oral doses of PyG (500 mg) twice daily for 3–4 days, oestradiol levels fell to 31.1%±6.3% of baseline values within 48 h and remained suppressed during treatment. Of a further six patients who received oral PyG (1 g) as a single dose, five had quantifiable oestradiol levels. Oestradiol suppression was sustained for 36 h and recovery correlated with a fall of PyG concentrations below a threshold value of ca. 2 g/ml. The pharmacokinetics of PyG were non-linear and, when fitted to the integrated Michaelis-Menten equation, yielded good parameter estimates forC _o (21.7±1.82 g/ml),K _m (2.66±0.68 g/ml) and V_max (0.86±0.06 g ml^–1 h^–1). On subsequent repeated dosing with PyG, both theK _m (4.31±0.48 g/ml) and the V_max (1.83±0.13 g ml^–1 h^–1) values increased and recovery from oestradiol suppression was more rapid, indicating that PyG induces its own metabolism.Abbreviations PyG 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione - AG aminoglutethimide - CSCC cholesterol side-chain cleavage - HPLC high-performance liquid chromatography - AUC area under the concentration versus time curve This study was supported in part by grants to the Institute of Cancer Research (Royal Cancer Hospital) from the Cancer Research Campaign and Medical Research Council     

Kinetic study of smoking marijuana

Six subjects each smoked a 1% marijuana cigarette and 2 hr later smoked a second one. Plasma levels of delta-9-tetrahydrocannabinol were measured for 9 hr with a radioimmunoassay. Heart rate and self-reported "high" were measured for 2 hr after each cigarette. All three measures showed a rapid increase after the start of smoking with Cmax occurring before the end of smoking. There was a strong correlation between decrease in heart rate and plasma levels from 10 min after smoking until 120 min. All pharmacodynamic response measures returned to baseline values within approximately 2 hr.     

Chronic lithium treatment inhibits pilocarpine-induced mossy fiber sprouting in rat hippocampus.

Lithium remains the gold standard in the treatment of bipolar disorder. Long-term treatment with lithium may lead to specific adaptational changes in gene expression that contribute to a neuroprotective effect. In this study, the pilocarpine model of spontaneous limbic epilepsy was used to induce mossy fiber sprouting (axonal growth of the dentate granule cells that synapse on the pyramidal cells of the CA3 region) to examine the prophylactic neuroprotective effects of lithium in vivo. There were four groups of animals: pilocarpine treated (Pil+/Li-); pilocarpine treated followed by lithium (Pil+/Li+); lithium alone (Pil-/Li+); control (Pil-/Li-). Timm staining was used to obtain density measurements in the stratum oriens and the inner molecular layer of the hippocampus. Mossy fiber density was higher in the pilocarpine-treated animals compared to controls. Chronic lithium following pilocarpine treatment attenuated the density of mossy fibers but lithium alone had no effect. No changes in hilar volume or neuronal number were detected using stereological procedures. The ability of lithium to attenuate activation-induced reorganization in the hippocampus provides evidence for its role as a neuroprotective agent in an in vivo model that may be relevant to its clinical effects in bipolar disorder.