Ezetimibe added to ongoing statin therapy improves LDL-C goal attainment and lipid profile in patients with diabetes or metabolic syndrome.

This analysis of the Ezetimibe Add-on to Statin for Effectiveness (EASE) trial examined the effectiveness and safety of ezetimibe 10 mg added to ongoing statin therapy in patients with diabetes, metabolic syndrome without diabetes, or neither disorder who had low-density lipoprotein cholesterol (LDL-C) levels exceeding National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) goals. After six weeks of treatment, ezetimibe added to statin reduced LDL-C in patients with diabetes by 28%, metabolic syndrome by 24%, or neither by 26%, compared with a 3% reduction for placebo for each group. In each group, more patients receiving ezetimibe plus statin reached LDL-C goal (67-74%) compared with those receiving placebo plus statin (19-22%).

Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients.

Objective: To assess the lipid-altering efficacy and safety of ezetimibe/simvastatin single tablet product compared with rosuvastatin at the approved usual starting, next highest, and maximum doses.

Research Design And Methods: Double-blind, multicenter, 6-week, parallel-group study in hypercholesterolemic patients (n = 2959). Patients were randomized based on stratification by low-density lipoprotein cholesterol (LDL-C) levels to ezetimibe/simvastatin or rosuvastatin, respectively, at the usual starting (10/20 or 10 mg/day), the next highest (10/40 or 20 mg/day), and maximum doses (10/80 or 40 mg/day).

Attenuated response to stress and novelty and hypersensitivity to seizures in 5-HT4 receptor knock-out mice.

To study the functions of 5-HT4 receptors, a null mutation was engineered in the corresponding gene. 5-HT4 receptor knock-out mice displayed normal feeding and motor behaviors in baseline conditions but abnormal feeding and locomotor behavior in response to stress and novelty. Specifically, stress-induced hypophagia and novelty-induced exploratory activity were attenuated in the knock-out mice.

Minimal behavioral effects from moderate postnatal lead treatment in rats.

Developmental lead exposure continues to be a worldwide problem. This study investigated the behavioral effects resulting from developmental lead treatment in rats with corresponding physiological measures of lead exposure. Sprague-Dawley rats were treated with 350 ppm lead acetate from birth to weaning via the dam's drinking water.

Declines in stimulated striatal dopamine release over the first 32 h following microdialysis probe insertion: generalization across releasing mechanisms.

In a recent paper [R.R. Holson, J.

Behavioral effects of low-dose gestational day 11-13 retinoic acid exposure.

In a comparison article we report that maternal PO exposure to 2.5 mg/kg all-trans retinoic acid (RA) daily for 3 consecutive days over gestational days (GD) 11-13 produces a 10% reduction in weight of cerebellum at 4 weeks of age, not accompanied by other malformations. Here we report the results of a preliminary behavioral analysis of offspring exposed gestationally to RA as above.

A behavioral and neuroanatomical investigation of the lethality caused by gestational day 11-13 retinoic acid exposure.

In a companion article, we report that there is a sensitive period for all-trans retinoic acid (RA) lethality on gestational days (GD) 11-13. When dams were given 10 mg/kg RA daily for 3 consecutive days on GD 11-13, a number of pups were found dead in the home cage on the day of birth, and the remainder inevitably died due to an apparent inability to nurse. Here we report a set of experiments further investigating these effects.

Gestational retinoic acid exposure: a sensitive period for effects on neonatal mortality and cerebellar development.

This is the first in a series of studies investigating the developmental stage-specific neurobehavioral effects of all-trans retinoic acid (RA) exposure. Because high doses of this compound are known to be lethal to the developing organism, we first conducted a dose-response study to identify RA doses that produce low enough levels of gestational/postnatal mortality to make a behavioral analysis possible in survivors. Secondarily, at doses found to produce sufficient survivors on PND 28, effects on body and regional brain weights were examined.

The effects of bupropion in vivo in the neostriatum of 5-day-old and adult rats.

Infusion of six concentrations of the dopamine uptake inhibitor bupropion into the neostriatum increased extracellular dopamine in a dose-dependent manner in 5-day-old and adult rats. There was no age-related difference when calculated as a percentage of predrug dopamine baseline levels, but the absolute increase of dopamine was greater in the adult rats. Bupropion had only a minor effect on extracellular levels of DOPAC.

Effects of (-)-sulpiride on dopamine release in striatum of developing rats: degree of depolarization influences responsiveness.

The purpose of this study was to determine the effects of localized delivery of the D2 antagonist (-)-sulpiride (via microdialysis) on spontaneous and evoked dopamine release in the neostriatum of urethane-anesthetized rats 5, 10, 15, 21, and 70 days of age. Sulpiride increased spontaneous dopamine release approximately threefold relative to baseline measures, and this effect decreased with maturation. The relationship between sulpiride- and potassium-evoked release was complex; sulpiride increased evoked dopamine outflow at 5, 10, and 15 days of age.

Calcium dependency and tetrodotoxin sensitivity of neostriatal dopamine release in 5-day-old and adult rats as measured by in vivo microdialysis.

The calcium dependency and tetrodotoxin sensitivity of extracellular dopamine levels were assessed by microdialysis in the neostriatum of 5-day-old rat pups and were compared with those obtained in adult rats. The removal of calcium from the dialysate reduced spontaneous levels of extracellular dopamine to 20% of normal in the 5-day-old pups and to 10% of normal in the adults. Calcium-free dialysate also decreased potassium-evoked dopamine release to approximately 20% of baseline in both ages.

The development of D2 autoreceptor-mediated modulation of K(+)-evoked dopamine release in the neostriatum.

A within-subject dose-response analysis was conducted by locally perfusing increasing concentrations (0.1, 1, 10 and 100 microM) of the selective D2 agonist quinpirole via a microdialysis probe into the neostriatum of urethane-anesthetized rat pups 5, 10-11, 15-16 and 21-22 days of age and adult rats. In Expt.

The ontogeny of apomorphine-induced alterations of neostriatal dopamine release: effects on potassium-evoked release.

The effects of apomorphine (0.05, 0.1, and 1.

The ontogeny of apomorphine-induced alterations of neostriatal dopamine release: effects on spontaneous release.

The effects of apomorphine (0.05, 0.1, and 1.

Effect of milk on dopamine release in the newborn rat: an in vivo microdialysis study.

Newborn rats exhibit a rich behavioral repertoire to access the nipple and obtain milk. In older pups, catecholamines including dopamine (DA) mediate the behavioral effects of milk. In the present study, pups were delivered at term by caesarean section and instrumented with the microdialysis probe.

Effects of phencyclidine on extracellular levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid in conscious and anesthetized rats.

Dose-dependent effects of phencyclidine on extracellular levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the neostriatum were studied in both urethane-anesthetized and conscious rats. In vivo microdialysis was used to collect 10 min samples that were analyzed for levels of DA, DOPAC and HVA, using high-performance liquid chromatography with electrochemical detection (HPLC-EC). In both the anesthetized and conscious preparations, 20 mg/kg of phencyclidine produced an increase in extracellular levels of DA, 10 mg/kg resulted in no change, while 1 mg/kg produced a slow decrease.

Inhibition of dopamine release by methylenedioxymethamphetamine is mediated by serotonin.

(+/-)-3,4-Methylenedioxymethamphetamine (MDMA), at doses of 0.1, 1 and 10 mg/kg, produced a long-lasting decrease in extracellular dopamine concentration in the neostriatum of anesthetized rats, as measured by in vivo voltammetry. Since MDMA has been shown to release serotonin from rat brain slices and synaptosomes, we examined the possibility that increased serotonin release might be the cause of the decrease in dopamine release.

Phenylcyclohexylamine: effect of a metabolite of phencyclidine on the efflux of dopamine in the rat.

The effect of phenylcyclohexylamine (PCA) on the efflux of dopamine (DA) in the neostriatum was examined using in vivo electrochemical techniques. Phenylcyclohexylamine produced a long-lasting dose-dependent biphasic effect on the efflux of DA in the rat. This response, to one of the major metabolites of phencyclidine, was similar in duration to but less potent than that seen with phencyclidine.

Physiological and morphological analyses of ventral anterior and ventral lateral thalamic neurons in the cat.

Intracellular recordings were made from ventral anterior and ventral lateral (VA-VL) thalamic neurons in the cat. VA-VL neurons were tested for responsiveness to activation of cortical, pallidal and cerebellar afferents, and were identified morphologically by intracellular injection of HRP. Orthodromic activation of cortical and pallidal afferents produced primarily an initial inhibition (due in part to oligosynaptic circuitry) while activation of cerebellar afferents produced an initial excitation in the majority of neurons tested.

The ontogeny of amphetamine-induced dopamine release in the caudate-putamen of the rat.

Amphetamine-induced dopamine (DA) release in the caudate-putamen of adult rats was compared with that in the 35-36-day-old and 21-22-day-old rat pup, using in vivo voltammetry. In the adult and 35-36-day groups, 1.0 mg/kg amphetamine (AMP) produced a significant increase in DA release, while 0.

3H-xylamine binds to presynaptic rat striatal membranes.

3H-xylamine (3H-XYL), an irreversible catecholamine uptake inhibitor, was incubated with rat striatal synaptosomes, and the membrane fraction was examined by fluorography of a sodium dodecyl sulfate-polyacrylamide gel. A number of peptides were labeled. To determine their location, the striatal dopaminergic presynaptic nerve terminals were destroyed by unilateral electrolytic lesions through the nigrostriatal fibers prior to 3H-XYL exposure.

Postnatal development of caudate input neurons in the cat.

Lectin-bound horseradish peroxidase (WG-HRP) was pressure-injected into the caudate nucleus (Cd) of neonatal (less than 24 hours of age) and adult cats in order to assess the postnatal development of monosynaptic Cd input neurons. Tissue was processed for peroxidase activity with a benzidine dihydrochloride chromagen. The injection of WG-HRP produced relatively similar labelled zones of marker uptake in the caudate nuclei of both neonates and adults.

Early postnatal x-irradiation of the hippocampus and discrimination learning in adult rats.

Rats with X-irradiation-produced degranulation of the hippocampal dentate gyrus were trained in the acquisition and reversal of simultaneous visual and tactile discriminations in a T-maze. These experiments employed the same treatment, apparatus, and procedure but varied in task difficulty. In the brightness and roughness discriminations, the irradiated rats were not handicapped in acquiring or reversing discriminations of low or low-moderate task difficulty.