No abstract

Biogenic amines, such as serotonin and dopamine, can be important in reinforcing associative learning. This function is evident as changes in memory performance with manipulation of either of these signals. In the insects, evidence begins to argue for a common role of dopamine in negatively reinforced memory. In contrast, the role of the serotonergic system in reinforcing insect associative learning is either unclear or controversial. We investigated the role of both of these signals in operant place learning in Drosophila. By genetically altering serotonin and dopamine levels, manipulating the neurons that make serotonin and dopamine, and pharmacological treatments we provide clear evidence that serotonin, but not dopamine, is necessary for place memory. Thus, serotonin can be critical for memory formation in an insect, and dopamine is not a universal negatively reinforcing signal.biogenic amines ͉ dopamine ͉ learning ͉ white-ABC transporter ͉ reinforcement T he neural systems containing biogenic amines, such as dopamine and serotonin, may mediate reinforcement information to influence memory performance. In the monkey for example, activity in the dopaminergic system is modulated based on expected reward (1), and the phasic output of these neurons may regulate memory performance (1, 2). In some invertebrates the biogenic amines have also been shown to be critical for conditioning (3)(4)(5). Within the insects, however, dopamine is the only biogenic amine clearly implicated in negatively reinforced associative memory (6-8). Indeed, and interestingly, dopaminergic system activation can be a sufficient reinforcing signal for olfactory conditioning in Drosophila larvae (9). Thus, support grows for a general function of the dopaminergic system in negatively reinforced memory. Whether serotonin has a role in insect learning is less clear (10), and in Drosophila it is controversial (11-13). Here, we investigated the influence of serotonin and dopamine on reinforcement of place learning in Drosophila.The ''heat box'' can be used to rapidly condition place memories in Drosophila (14,15). In this paradigm, single flies are allowed to wander in a chamber that is lined top and bottom with Peltier heating elements ( Fig. 1) (16, 17). A series of light sensors on one side of the chamber tracks the behavior of a fly, and when the animal moves to a predetermined half, the whole chamber heats to a nonpreferred (aversive) temperature. With experience, normal flies avoid the chamber-half associated with rising temperatures (15,16,18). A test performed after conditioning, when the danger of rising temperature is removed, is used to measure place memory. Importantly, one can dissociate acquisition from reinforcement processing defects by the performance of mutant flies after short and long training sessions (19). Flies that are mutant for a type-1 adenylyl cyclase (i.e., rutabaga) show poor memory performance after short periods of conditioning but normal memory after longer training, emphasizing the memory acquisition function for...

ObjectiveDaily adult human exposure to bisphenol A (BPA) has been estimated at < 1 μg/kg, with virtually complete first-pass conjugation in the liver in primates but not in mice. We measured unconjugated and conjugated BPA levels in serum from adult female rhesus monkeys and adult female mice after oral administration of BPA and compared findings in mice and monkeys with prior published data in women.MethodsEleven adult female rhesus macaques were fed 400 μg/kg deuterated BPA (dBPA) daily for 7 days. Levels of serum dBPA were analyzed by isotope-dilution liquid chromatography–mass spectrometry (0.2 ng/mL limit of quantitation) over 24 hr on day 1 and on day 7. The same dose of BPA was fed to adult female CD-1 mice; other female mice were administered 3H-BPA at doses ranging from 2 to 100,000 μg/kg.ResultsIn monkeys, the maximum unconjugated serum dBPA concentration of 4 ng/mL was reached 1 hr after feeding and declined to low levels by 24 hr, with no significant bioaccumulation after seven daily doses. Mice and monkeys cleared unconjugated serum BPA at virtually identical rates. We observed a linear (proportional) relationship between administered dose and serum BPA in mice.ConclusionsBPA pharmacokinetics in women, female monkeys, and mice is very similar. By comparison with approximately 2 ng/mL unconjugated serum BPA reported in multiple human studies, the average 24-hr unconjugated serum BPA concentration of 0.5 ng/mL in both monkeys and mice after a 400 μg/kg oral dose suggests that total daily human exposure is via multiple routes and is much higher than previously assumed.

A method for analysis of ergovaline in seed and vegetative tissue of endophyte-infested tall fescue by high-performance liquid chromatography with fluorescence detection was developed. Freeze-dried samples were extracted with alkaline chloroform, filtered, and applied to disposable HL silica gel columns. Following elution of plant pigments with acetone/chloroform, ergopeptine alkaloids were eluted with methanol under vacuum. Column eluant was evaporated to near dryness and the residue redissolved in methanol/water and analyzed by high-performance liquid chromatography; ergotamine was the internal standard. Average recoveries of ergovaline and ergotamine were 85 and 88%, respectively, with a relative standard deviation of 7.5%. The detection limit of ergovaline in fescue seed and vegetative tissue was 50 pg/kg. Replicate samples, collected each week during two growing seasons from experimental plots of KY-31 tall fescue (85-100'3 endophyte-infested), were separated into stems with leaf sheaths, leaf blades, and developing seed heads. Ergovaline levels in all plant tissues were 300-

The objective of the present study was to evaluate the efficacy of curcumin, an antioxidant found in turmeric (Curcuma longa) powder (TMP), to ameliorate changes in gene expression in the livers of broiler chicks fed aflatoxin B(1) (AFB(1)). Four pen replicates of 5 chicks each were assigned to each of 4 dietary treatments, which included the following: A) basal diet containing no AFB(1) or TMP (control), B) basal diet supplemented with TMP (0.5%) that supplied 74 mg/kg of curcumin, C) basal diet supplemented with 1.0 mg of AFB(1)/kg of diet, and D) basal diet supplemented with TMP that supplied 74 mg/kg of curcumin and 1.0 mg of AFB(1)/kg of diet. Aflatoxin reduced (P < 0.05) feed intake and BW gain and increased (P < 0.05) relative liver weight. Addition of TMP to the AFB(1) diet ameliorated (P < 0.05) the negative effects of AFB(1) on growth performance and liver weight. At the end of the 3-wk treatment period, livers were collected (6 per treatment) to evaluate changes in the expression of genes involved in antioxidant function [catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST)], biotransformation [epoxide hydrolase (EH), cytochrome P450 1A1 and 2H1 (CYP1A1 and CYP2H1)], and the immune system [interleukins 6 and 2 (IL-6 and IL-2)]. Changes in gene expression were determined using the quantitative real-time PCR technique. There was no statistical difference in gene expression among the 4 treatment groups for CAT and IL-2 genes. Decreased expression of SOD, GST, and EH genes due to AFB(1) was alleviated by inclusion of TMP in the diet. Increased expression of IL-6, CYP1A1 and CYP2H1 genes due to AFB(1) was also alleviated by TMP. The current study demonstrates partial protective effects of TMP on changes in expression of antioxidant, biotransformation, and immune system genes in livers of chicks fed AFB(1). Practical application of the research is supplementation of TMP in diets to prevent or reduce the effects of aflatoxin in chicks fed aflatoxin-contaminated diets.