Biomedical subjects

A J Roberts

Publications and source records attributed to A J Roberts.

At least 19 recordsLinked to original sources

PubMed2001

Sequence evaluation of four pooled-tissue normalized bovine cDNA libraries and construction of a gene index for cattle.

An essential component of functional genomics studies is the sequence of DNA expressed in tissues of interest. To provide a resource of bovine-specific expressed sequence data and facilitate this powerful approach in cattle research, four normalized cDNA libraries were produced and arrayed for high-throughput sequencing. The libraries were made with RNA pooled from multiple tissues to increase efficiency of normalization and maximize the number of independent genes for which sequence data were obtained. Target tissues included those with highest likelihood to have impact on production parameters of animal health, growth, reproductive efficiency, and carcass merit. Success of normalization and inter- and intralibrary redundancy were assessed by collecting 6000-23,000 sequences from each of the libraries (68,520 total sequences deposited in GenBank). Sequence comparison and assembly of these sequences was performed in combination with 56,500 other bovine EST sequences present in the GenBank dbEST database to construct a cattle Gene Index (available from The Institute for Genomic Research at http://www.tigr.org/tdb/tgi.shtml). The 124,381 bovine ESTs present in GenBank at the time of the analysis form 16,740 assemblies that are listed and annotated on the Web site. Analysis of individual library sequence data indicates that the pooled-tissue approach was highly effective in preparing libraries for efficient deep sequencing.

Animals↗

PubMed2001

A re-analysis of a caries clinical trial by survival analysis.

The decline in caries prevalence, the increases in the level of fluoride exposure, and the lack of placebo control subjects have complicated caries clinical trials in recent times. There has been a substantial increase in the numbers of subjects required for the detection of statistically significant differences between dental products, and hence, the cost of these trials has grown enormously. This study uses a new statistical approach to the analysis of the data from these trials with the ultimate aim of providing a more sensitive method of analysis. The new approach uses survival analysis, where the outcome measure is the survival time of an individual tooth surface. It exploits recent developments in the analysis of clustered survival data where survival times within the same cluster or subject are correlated. To illustrate, the new method of analysis was used for the North Wales, UK, caries clinical trial. It is concluded that survival analysis uses most of the data available in a caries clinical trial, an outcome measure that is easily understood and may lead to a more sensitive method of analysis.

Analysis of Variance↗

PubMed2001

The role of craving in alcohol use, dependence, and treatment.

This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The organizer and chair was Barbara A. Flannery, and the co-chairs were Barbara A. Flannery and Helen Pettinati. The presentations were (1) Animal models of alcohol craving and relapse, by Amanda Roberts; (2) Real-time field assessment of alcohol craving, by Ned Cooney; (3) Medications and alcohol craving, by Robert Swift; (4) The assessment of craving: Insights from the clinic and clinical laboratory studies, by Raymond Anton; (5) A comparison of three alcohol craving questionnaires, by Barbara Flannery; (6) and Assessing posttreatment urge to drink, by Damaris Rohsenow.

Alcohol Drinking↗

PubMed2000

Excessive ethanol drinking following a history of dependence: animal model of allostasis.

Alcohol withdrawal symptoms, particularly negative emotional states, can persist for months following the removal of alcohol. These protracted withdrawal symptoms have been implicated as an important trigger of relapse to excessive drinking in alcoholics and may represent a long lasting shift in affective tone as a result of chronic alcohol exposure. It was shown previously that ethanol-dependent rats increased their operant responding for ethanol when tested during the first 12 hr after withdrawal. The purpose of the present experiments was to determine the persistence of this finding by examining operant oral ethanol self-administration in rats with a history of physical dependence upon ethanol, detoxified and then allowed a two week period of protracted abstinence. The results of these experiments indicate that operant responding for ethanol was enhanced during protracted abstinence by 30-100% and remained elevated for 4-8 weeks post acute withdrawal. These results have important implications for understanding the characteristics and mechanisms underlying vulnerability to relapse.

Alcohol Drinking↗

PubMed2000

Lactation and calf weight traits of mature crossbred cows fed varying daily levels of metabolizable energy.

Our objective was to evaluate differences in lactation traits and calf weights produced by F1 cows under varying daily metabolizable energy availability. Measures of milk yields and calf weight traits were recorded on mature F1 cows. The cows were produced from matings of Angus or Hereford dams with sires representing Angus/Hereford, Shorthorn, Galloway, Longhorn, Nellore, and Salers breeds. The cows' daily DM intakes of a diet composed of a corn silage or alfalfa silage plus corn silage were recorded from approximately 2 wk postpartum until the calves were weaned at an average age of 170 d. Milk yield measurements were recorded when the calves were approximately 14, 28, 56, 84, 112, 140, and 168 d of age. Sources of variation considered for the traits of interest included sire breed of the cow (SBC) and the covariates weaning age of the calf and daily metabolizable energy intake (DMEI) of the cow for lactation and calf weights. The linear and quadratic effects were evaluated for DMEI. The SBC x DMEI (linear) interaction was significant for total milk yield. Sire breed of cow differences (P < .05) were observed for milk yield at time of peak yield, persistency, preweaning ADG, and weaning weight. Salers- and Shorthorn-sired cows had greater (P < .05) peak yield than Galloway, Longhorn, or Nellore cross-bred cows but were not significantly different from the Hereford/Angus. Increasing DMEI linearly increased peak yield and total yield (P < .05). Preweaning ADG of calves from Nellore-sired cows was greater (P < .05) than all SBC. Preweaning ADG of calves from Galloway-sired cows was less than all SBC (P < .05). The linear effect of DMEI was heterogeneous across SBC for total yield. The pooled quadratic effect of DMEI was significant for all traits except birth weight. The DMEI for expression of maximum weaning weight was estimated to be 29 Mcal. Feed efficiency ratios for the test period were 28, 27, 30, 25, 28, 32, and 30 g calf weight:Mcal DMEI for reference and 1980s Angus/Hereford-, Shorthorn-, Galloway-, Longhorn-, Nellore-, and Salers-sired cows, respectively, at the DMEI level of 29 Mcal.

Animal Feed↗

PubMed2000

mu-Opioid receptor knockout mice do not self-administer alcohol.

Opioid peptides long have been hypothesized to play a role in ethanol reinforcement. Neuropharmacological studies have shown that opioid receptor antagonists decrease ethanol self-administration in rodents and prevent relapse in humans. However, the exact mechanism for such powerful effects has remained elusive. The availability of mu-opioid receptor knockout mice has made possible the direct examination of the role of the mu-opioid receptor in mediating ethanol self-administration. In the present experiments, both nosepoke and lever operant ethanol self-administration and several tests of two bottle-choice ethanol drinking were studied in these genetically engineered mice. In no case did knockout mice show evidence of ethanol self-administration, and, in fact, these mice showed evidence of an aversion to ethanol under several experimental conditions. These data provide new evidence for a critical role for mu-opioid receptors in ethanol self-administration assessed with a variety of behavioral paradigms and new insights into the neuropharmacological basis for ethanol reinforcement.

Alcohol Drinking↗

PubMed1999

Insulin-like growth factor-I, insulin-like growth factor-binding proteins, and gonadotropins in the hypothalamic-pituitary axis and serum of nutrient-restricted ewes.

Body condition scores (BCS) of ovariectomized estradiol-treated ewes were controlled to examine effects of suboptimum BCS on insulin-like growth factor (IGF)-I, IGF-binding proteins (IGFBPs), and LH in the anterior pituitary gland, hypophyseal stalk-median eminence (SME), and circulation. Serum LH increased in ewes with BCS (1 = emaciated, 9 = obese) > 3 (HIGH-BCS), but not in ewes with BCS </= 3 (LOW-BCS), after onset of the breeding season. Concentrations of LH and LHbeta subunits in anterior pituitary glands were lower in LOW-BCS than in HIGH-BCS ewes. Serum IGF-I was lower in LOW-BCS than in HIGH-BCS ewes but did not differ in SME or anterior pituitary glands. In serum, the 44-kDa IGFBP-3 and 24-kDa IGFBP-4 were lower in LOW-BCS than in HIGH-BCS ewes. In anterior pituitary glands, IGFBP-2 tended to be higher in LOW-BCS than in HIGH-BCS ewes. In the SME, IGFBP-2, -3, and -5 were lower in LOW-BCS than in HIGH-BCS ewes. Low body condition may inhibit the increased secretion of LH associated with the onset of the breeding season by altering relative amounts of IGFBPs within the hypothalamic-pituitary axis.

Animals↗

PubMed1999

Operant self-administration of sweetened versus unsweetened ethanol: effects on blood alcohol levels.

BACKGROUND: Sweeteners are often added to ethanol solutions to increase ethanol intake. However, literature on studies that use human subjects and laboratory animals suggests that sucrose, other sugars, and carbohydrate-rich foods alter ethanol absorption and metabolism, which leads to lower blood alcohol levels (BAL) relative to ethanol absorbed alone. This experiment was designed to test whether the addition of the nutritive sweetener sucrose, or the nonnutritive sweetener saccharin, to a 10% ethanol solution, self-administered in an oral operant paradigm, affected BAL in rats relative to self-administration of an unsweetened 10% ethanol solution. METHODS: All rats were trained to lever press for ethanol by use of a saccharin fading procedure. Half of the rats then received 30-min sessions in which ethanol + 2% sucrose and water were available and were alternated daily with sessions in which ethanol + 0.2% saccharin and water were available. The other half of the rats went on to receive daily sessions of unsweetened ethanol and water. BAL were taken after these standard daily sessions as well as after a 1-week period of alcohol deprivation (to enhance ethanol intake). RESULTS: Rats responded for more ethanol + sucrose than unsweetened ethanol, but had lower BAL per gram ethanol consumed in both the baseline test and alcohol deprivation effect test. No effect of saccharin on BAL was detected. An additional experiment that examined the effects of four concentrations of both sucrose and saccharin on self-administration of ethanol and BAL showed that, whereas rats consumed more ethanol + sucrose than ethanol + saccharin, BAL were significantly lower per gram ethanol consumed in the sucrose group. CONCLUSIONS: These results confirm previous reports and suggest that the addition of sucrose to an ethanol solution can result in lower BAL relative to unsweetened ethanol in an oral operant self-administration paradigm.

Alcohol Drinking↗

PubMed1999

Central administration of an opiate antagonist decreases oral ethanol self-administration in rats.

BACKGROUND: Opioid peptides have been implicated in various behavioral actions of alcohol, including its reinforcing effects; however, the role of specific brain sites for these actions remains to be explored. The present study examined the effects of intracerebroventricular (ICV) or intracerebral injections of an opiate antagonist (methylnaloxonium) on ethanol self-administration. The nucleus accumbens and amygdala were selected as intracerebral sites because these regions have been implicated in the reinforcing effects of drugs of abuse. METHODS: Male Wistar rats were trained in a limited-access paradigm (30 min/day) to respond for ethanol (10% w/v) or water in a two-lever free-choice condition using a saccharin fading procedure. After the establishment of stable baseline responding for ethanol, animals were implanted stereotaxically with a guide cannula above the lateral ventricle or with bilateral guide cannulae either above the nucleus accumbens or amygdala. After postoperative recovery of stable baseline responding, the rats were tested 15 min after ICV or intracerebral microinjections of methylnaloxonium (0-2000 ng). RESULTS: Injections of methylnaloxonium into the amygdala significantly reduced responding for ethanol at doses of 250-500 ng. Injections of methylnaloxonium into the nucleus accumbens significantly reduced responding for ethanol at doses of 500-1000 ng, whereas higher doses were needed ICV. CONCLUSIONS: These results provide evidence that opioid receptors located in the amygdala and nucleus accumbens may be involved in the regulation of ethanol self-administration.

Amygdala↗

PubMed1999

Cannabinoid receptor antagonist SR141716A decreases operant ethanol self administration in rats exposed to ethanol-vapor chambers.

AIM: To study the potential role of dependence status on CB1-mediated blockade of ethanol self-administration. METHODS: We examined the effects of the cannabinoid antagonist SR141716A (0, 0.03, 0.3, and 3 mg/kg) on operant ethanol (10% v/v) self-administration in male Wistar rats that were made ethanol-dependent by chronic (14 d) exposure to ethanol vapor-chambers or exposed to air in identical vapor chambers. RESULTS: Dependent animals responded more for ethanol than did air control nondependent rats. The acute administration of a 3 mg/kg dose of SR141716A almost suppressed ethanol self-administration only in ethanol dependent animals. However, operant responses for food were not affected by the administration of SR141716A. CONCLUSION: These results further support that cannabinoid CB1 receptor blockade may have a potential utility for the treatment of alcoholism.

Alcoholism↗

PubMed1998

CB1 cannabinoid receptor antagonist-induced opiate withdrawal in morphine-dependent rats.

Recent reports have provided evidence of a link between the endogenous brain cannabinoid system and the endogenous central opioid systems. Here we report that the selective CB1 receptor antagonist SR 141716A induced behavioral and endocrine alterations associated with opiate withdrawal in morphine-dependent animals in a dose-dependent manner and that naloxone induced an opiate withdrawal syndrome in animals made cannabinoid-dependent by repeated administration of the potent cannabinoid agonist HU-210. Additionally CB1 and mu-opioid receptor mRNAs were co-localized in brain areas relevant for opiate withdrawal such as the nucleus accumbens, septum, dorsal striatum, the central amygdaloid nucleus and the habenular complex. These results suggest that CB1 cannabinoid receptors may play a role in the neuroadaptive processes associated with opiate dependence, and they lend further support for the hypothesis of a potential role of cannabinoid receptors in the neurobiological changes that culminate in drug addiction.

Animals↗

PubMed1998

Effects of amperozide, 8-OH-DPAT, and FG 5974 on operant responding for ethanol.

Both 5-HT1A and 5-HT2A receptors have been implicated in modulating ethanol self-administration. A novel serotonergic compound, FG 5974, with combined 5-HT1A agonist/5-HT2A antagonist activities, has shown effects in decreasing ethanol consumption in two-bottle choice paradigms. In the present study, the effect of this compound on operant responding for ethanol (as well as water and a saccharin solution) was compared to compounds possessing the separate neuropharmacological effects of this drug (the 5-HT1A agonist, 8-OH-DPAT, and the 5-HT2A antagonist, amperozide). While all three serotonergic compounds decreased operant responding for ethanol, only FG 5974 had no effect on water and saccharin responding. These results suggest that combined 5HT1A agonist/5-HT2A antagonist activity provides a more selective effect on ethanol reinforcement than either neuropharmacological action alone. Therefore, further analysis of mixed serotonergic compounds in general, and FG 5974 in particular, is warranted as they offer potential treatments for alcoholism.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1998

Estradiol increases relative amounts of insulin-like growth factor binding protein (IGFBP)-3 in serum and expression of IGFBP-2 in anterior pituitaries of ewes.

This study determined whether estradiol regulates insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBPs) in the pituitary gland, hypophyseal stalk median eminence (SME), and circulation concomitantly with effects on LH. Ovariectomized ewes received an estradiol implant or no implant during the anestrous season and were slaughtered 80 days later. Estradiol suppressed serum LH to a greater extent during anestrus than after onset of the breeding season (Days 60 and 75). Amounts of mRNA for LHbeta subunit were decreased by estradiol, but mRNA for alpha and FSHbeta subunits were not affected. Estradiol increased serum IGF-I, IGFBP-3, and IGFBP-4 throughout the treatment period, but it did not influence other IGFBPs in serum. In response to estradiol, pituitary IGFBP-2 tended to increase and mRNA for IGFBP-2 increased twofold. Other IGFBPs in the pituitary gland were not influenced by estradiol. In the SME, IGFBP-2, IGFBP-5, and the 40-kDa IGFBP-3 were increased by estradiol. Thus, estradiol influences both the IGF and gonadotropin systems in sheep. Estradiol influences on gonadotroph function may be mediated by alterations in the IGF system.

Animals↗

PubMed1998

Characterization of insulin-like growth factor-binding proteins in the uterus and conceptus during early conceptus elongation in cattle.

As a first step in determining the role that insulin-like growth factor (IGF)-binding proteins (BPs) may have in regulating initial stages of conceptus elongation in cattle, the type and relative abundance of IGFBPs in serum, uterine tissues, and uterine fluid from pregnant and noninseminated cows on Days 13 and 15 postestrus and in Day 15 conceptuses was evaluated. Uterine and serum samples contained IGFBPs 2, 3, 4, and 5 as determined by immunoprecipitation followed by Western ligand blots of precipitates. Compared with those in uterine and serum samples, IGFBPs in conceptuses and conceptus-conditioned culture media were only faintly detectable. The percentage of the total IGF-I binding activity attributed to IGFBP-3 was greater (p < 0.05) in myometrium, serum, and uterine fluid (> 50%) than in inter- (40%) and intracaruncular (37%) endometrium. Percentage of total binding attributed to IGFBP-2 was greater (p < 0.05) in endometrium and serum ( approximately 30%) than in myometrium (16%) and uterine fluid (9%). Binding activity of certain IGFBPs varied due to day of the estrous cycle or due to pregnancy status. Concentrations of IGF-I in serum were greater (p < 0.05) in nonpregnant (52 +/- 2 ng/ml) than in pregnant (40 +/- 4 ng/ml) cows. Concentration of IGF-I in uterine fluid did not differ due to pregnancy status or stage of cycle (4.4 pg IGF-I/ microg uterine protein). Northern blots revealed mRNAs for IGFBPs 1, 2, 3, 4, and 5 in uterine tissues but not in conceptuses. In situ hybridization indicated that IGFBP-1 mRNA was primarily localized in luminal epithelium of endometrium; IGFBP-2 mRNA was in luminal epithelium and dense stromal cells adjacent to endometrial epithelium; and IGFBP-3 mRNA was in vascular endothelial cells and was more prevalent in myometrium than in endometrium. Tissue specificity and changes in abundance of IGFBPs in the uterus during early conceptus elongation indicate the potential importance of IGFBP regulation of uterine IGFs during this time period.

Animals↗

PubMed1998

Substance dependence as a compulsive behavior.

A compulsion to take a drug combined with a loss of control in limiting intake is the defining feature of substance dependence or addiction, and is the conceptual framework for the criteria of substance dependence or addiction outlined by the World Health Organization and the American Psychiatric Association. However, defining exactly what constitutes loss of control and compulsive drug taking at the level of animal models is a daunting task, and it is clear that no validated animal model exists for the whole syndrome of addiction. The present discussion redefines loss of control as a narrowing of the behavioral repertoire toward drug-seeking behavior and suggests that there are many sources of reinforcement that contribute to this behavioral focus on drug seeking. Evidence is presented demonstrating separate animal models for many of these sources of reinforcement as well as for most of the criteria for substance dependence. Evidence is also presented showing that the brain neurochemical systems involved in processing drug reward are altered by chronic drug exposure to contribute additional sources of reinforcement. Challenges for the future involve not only elucidation of the neurobiological substrates of the different behavioral components of addiction, but better animal models of these components with which to effect such studies.

Animals↗

PubMed1998

Growth, body composition, and endocrine responses to chronic administration of insulin-like growth factor I and(or) porcine growth hormone in pigs.

The actions of IGF-I, alone and in combination with porcine growth hormone (pGH), on growth and circulating endocrines and metabolites important in growth were investigated in peripubertal-age Meishan barrows. Pigs were assigned to four treatments: control, buffer; IGF-I, 33 microg rhIGF-I/kg BW injected twice daily; pGH, 33 microg rpGH/kg BW injected once daily; and IGF-I+pGH, 33 microg rhIGF-I/kg BW injected twice daily plus 33 microg rpGH/kg BW injected once daily. Treatments were administered for 28 d. Feed intake, BW, and backfat were recorded and blood samples were collected weekly. At slaughter, organ and primal cut weights were recorded. Offal and half the carcass were ground for chemical analysis. Serum concentrations of IGF-I on d 7, 14, 21, and 28 in the IGF-I, pGH, and IGF-I+pGH groups were increased 60, 107, and 131%, respectively, compared with those of the control group. Administration of pGH increased gain 43%, feed efficiency 60%, carcass protein accretion 88%, and trimmed lean cuts 16%, whereas IGF-I administration increased gain 22%, carcass protein accretion 33%, and trimmed lean cuts 5%. There was little difference in responses to administration of IGF-I+pGH and pGH alone except that coadministration of IGF-I with pGH reduced the ability of pGH to suppress backfat gain (P < .02). Even though administration of IGF-I resulted in a 60% increase in chronic nadir serum concentrations of IGF-I, only a few growth and carcass measures were changed when compared with control pigs. These included increased (P < .05) weight of body, leaf fat, kidneys, and belly. The actions of pGH on growth of pigs were not mimicked, and some were countermanded by administration of IGF-I at a dose that produces significantly increased serum concentrations of IGF-I.

Animals↗

PubMed1998

Neurocircuitry targets in ethanol reward and dependence.

Alcoholism is a complex behavioral disorder characterized by excessive consumption of ethanol, a narrowing of the behavioral repertoire toward excessive consumption, the development of tolerance and dependence, and impairment in social and occupational functioning. Animal models of the complete syndrome of alcoholism are difficult if not impossible to achieve, but validated animal models exist for many of the different components of the syndrome. Recent work has begun to define the neurocircuits responsible for the two major sources of reinforcement key to animal models of excessive ethanol intake: positive and negative reinforcement. Ethanol appears to interact with ethanol-sensitive elements within neuronal membranes that convey the specificity of neurochemical action. Ethanol reinforcement appears to be mediated by an activation of GABA-A receptors, release of opioid peptides, release of dopamine, inhibition of glutamate receptors, and interaction with serotonin systems. These neurocircuits may be altered by chronic ethanol administration as reflected by opposite effects during acute ethanol withdrawal and by the recruitment of other neurotransmitter systems such as the stress neuropeptide corticotropin-releasing factor. Future challenges will include a focus on understanding how these neuroadaptive changes convey vulnerability to relapse in animals with a history of ethanol dependence.

Alcohol Drinking↗

PubMed1998

Estrous cycle effects on operant responding for ethanol in female rats.

Human females have been reported to be uniquely sensitive to the deleterious effects of ethanol, thus it is important to study the characteristics of and mechanisms underlying alcohol consumption that may be specific to females. Models of ethanol self-administration in female rats that take into consideration the estrous cycle have the potential to provide important information concerning these characteristics and mechanisms. The purpose of this study was to explore the effect of the cycle on ethanol self-administration using a limited access operant paradigm. Female Wistar rats were trained to lever press for 10% ethanol versus water using a saccharin fading procedure. Responses were examined across the four phases of the estrous cycle. No effects of estrous cycle phase were observed when these rats were allowed to cycle freely. Subsequently, estrous phase effects were investigated in females whose cycles had been synchronized. Under this condition, an effect of estrous phase was present, with lower ethanol intake observed in estrus (and in some cases proestrus). Synchronized rats all showed at least one very clear 4-day estrous cycle, whereas free-running rats' cycles ranged from 3 to 5 days. Thus, it is more likely that synchronized rats were tested in the identical portion of each phase, when hormone levels were less variable. These results suggest that ethanol may be more reinforcing during diestrus than proestrus and estrus in female rats.

Alcohol Drinking↗