The 5-HT indirect agonist, d-fenfluramine, attenuates cue reinstatement of extinguished cocaine-seeking behavior. To investigate the role of 5-HT receptor subtypes in this effect, we examined whether the attenuation is reversed by either a 5-HT 1A , 5-HT 2A/C , or 5-HT 2C receptor antagonist. We also examined the effects of the antagonists alone on both cue and cocaine-primed reinstatement. Rats that had been trained to press a lever for cocaine (0.75 mg/kg/0.1 ml, i.v.) paired with light and tone cues underwent daily extinction sessions during which responding had no consequences. We then examined the effects of WAY 100635 (0-1.0 mg/kg, s.c.), ketanserin (0-10.0 mg/kg, i.p.), or SB 242,084 (0-1.0 mg/kg, i.p.) with and without d-fenfluramine (1.0 mg/kg, i.p.) pretreatment on cue reinstatement. Subsequently, we examined the effects of the antagonists on cocaine-primed (7.5 or 15.0 mg/kg, i.p.) reinstatement. The 5-HT 1A antagonist, WAY 100635, failed to alter cue reinstatement, but attenuated cocaine reinstatement. Conversely, the 5-HT 2A/C antagonist, ketanserin, attenuated cue reinstatement, but failed to alter cocaine reinstatement. The 5-HT 2C -selective antagonist, SB 242,084, did not alter cue or cocaine reinstatement, but was the only drug that reversed the d-fenfluramine-induced attenuation of cue reinstatement. The findings suggest that stimulation of 5-HT 1A receptors plays a critical role in cocaine-primed, but not cue, reinstatement. Furthermore, 5-HT 2A and 5-HT 2C receptors may play oppositional roles in cue reinstatement. The SB 242,084 reversal of the d-fenfluramine attenuation suggests that stimulation of 5-HT 2C receptors inhibits cue reinstatement, whereas the ketanserin-induced attenuation of cue reinstatement suggests that decreased stimulation of 5-HT 2A receptors inhibits this behavior.

While the antagonist and full agonist produced similar effects on cocaine-seeking behavior, only the agonist increased response latency, suggesting that different processes mediate the effects of these drugs.

Brain-derived neurotrophic factor (BDNF) has been directly related to exercise-enhanced motor performance in the neurologically injured animal model; however literature concerning the role of BDNF in the enhancement of motor learning in the human population is limited. Previous studies in healthy subjects have examined the relationship between intensity of an acute bout of exercise, increases in peripheral BDNF and motor learning of a simple isometric upper extremity task. The current study examined the role of high intensity exercise on upregulation of peripheral BDNF levels as well as the role of high intensity exercise in mediation of motor skill performance and retention of a novel locomotor task in neurologically intact adults. In addition, the impact of a single nucleotide polymorphism in the BDNF gene (Val66Met) in moderating the relationship between exercise and motor learning was explored. It was hypothesized that participation in high intensity exercise prior to practicing a novel walking task (split-belt treadmill walking) would elicit increases in peripheral BDNF as well as promote an increased rate and magnitude of within session learning and retention on a second day of exposure to the walking task. Within session learning and retention would be moderated by the presence or absence of Val66Met polymorphism. Fifty-four neurologically intact participants participated in two sessions of split-belt treadmill walking. Step length and limb phase were measured to assess learning of spatial and temporal parameters of walking. Serum BDNF was collected prior to and immediately following either high intensity exercise or 5 minutes of quiet rest. The results demonstrated that high intensity exercise provides limited additional benefit to learning of a novel locomotor pattern in neurologically intact adults, despite increases in circulating BDNF. In addition, presence of a single nucleotide polymorphism on the BDNF gene did not moderate the magnitude of serum BDNF increases with high intensity exercise, nor did it moderate the relationship between high intensity exercise and locomotor learning.

No abstract

Inflammation and oxidative stress are important factors in the development of cardiovascular disease and atherosclerosis. The findings of our previous study suggest that 12 weeks consumption of tart cherry juice lowers the levels of systolic blood pressure (BP) and low-density lipoprotein (LDL) cholesterol in older adults. The present study investigated the effects of tart cherry juice on blood biomarkers of inflammation and oxidative stress. In this randomized-controlled clinical trial, a total of 37 men and women between the ages of 65–80 were randomly assigned to consume 480 mL of tart cherry juice or control drink daily for 12 weeks. Several blood biomarkers of inflammation and oxidative stress were assessed at baseline and after 12 weeks intervention. After the 12 weeks intervention, tart cherry juice significantly increased the plasma levels of DNA repair activity of 8-oxoguanine glycosylase (p < 0.0001) and lowered (p = 0.03) the mean c-reactive protein (CRP) level compared to the control group. There was a significant group effect observed for plasma CRP (p = 0.03) and malondialdehyde (MDA) (p = 0.03), and a borderline significant group effect observed for plasma oxidized low-density lipoprotein (OxLDL) (p = 0.07). Within group analysis showed that the plasma levels of CRP, MDA, and OxLDL decreased numerically by 25%, 3%, and 11%, respectively after 12 weeks of tart cherry juice consumption compared with corresponding baseline values. The present study suggests that the ability of tart cherry juice to reduce systolic BP and LDL cholesterol, in part, may be due to its anti-oxidative and anti-inflammatory properties. Larger and longer follow-up studies are needed to confirm these findings.

The findings suggest that the attenuating effects of D1-receptor drugs on cocaine-seeking behavior during cocaine reinstatement are mediated by dopamine D1 receptors; however, it remains unclear whether the effects of these drugs on cocaine-seeking behavior during cue reinstatement are D1-receptor mediated. Nevertheless, it is evident that the attenuation of cocaine-seeking behavior by these drugs is not simply due to behavioral disruption.

Men reported symptom severity at pretreatment and posttreatment as low to moderate. There were significant differences from pretreatment to posttreatment in fatigue, insomnia, urinary irritative and incontinence, bowel, sexual, and hormonal problems. There were no significant differences in TNF-α, IL-6, IL-10, or IL-4. At pretreatment, TNF-α was associated with depression, anxiety, urinary irritative, and bowel problems, and IL-4 was related to urinary irritative symptoms. At posttreatment, IL-4 was associated with urinary irritative symptoms. Findings suggest that, in men with prostate cancer, there is no strong association between symptom reporting and cytokine levels. Ongoing research focused on neuroendocrine and genetic markers and their associations with symptoms is promising and may result in the provision of better markers for quantifying the symptom experience in patients with cancer.

Antibody against purified bovine cathepsin D was raised in rabbits, and the polyclonal antiserum was tested to determine its ability to inhibit the hemoglobinolytic activity of the crude enzyme preparation (CEP) from adult Schistosoma japonicum and its effect upon in vitro cultured Schistosoma mansoni schistosomules. The 100,000 g supernatant fraction (CEP) from lyophilized adult worms was preincubated with antiserum and subsequently incubated with hemoglobin. Hemoglobinolytic activity was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoretic procedures. Five hours of incubation failed to diminish hemoglobin concentration in experimentals, whereas controls treated with preimmune serum displayed hemoglobin degradation. Pepstatin inhibited hemoglobin degradation. Western blot analysis of the CEP revealed a broad band of activity at approximately 45 kDa. Schistosomules incubated in vitro either in the antiserum or pepstatin and subsequently exposed to host erythrocytes showed a marked inhibition of digestive activities. Although structural changes were not evident in the gastrodermis, some perturbation of the tegument was observed. Schistosomules fed host erythrocytes and postincubated in the antiserum displayed increased tegumental perturbation and extensive alteration of the gastrodermis, including dilation of cisternae and membrane disruption. Schistosomules exposed to preimmune serum were normal in all respects.