Biomedical subjects

C A Moody

Publications and source records attributed to C A Moody.

At least 19 recordsLinked to original sources

PubMed2001

Determination of perfluorinated surfactants in surface water samples by two independent analytical techniques: liquid chromatography/tandem mass spectrometry and 19F NMR.

Perfluorinated surfactants are an important class of specialty chemicals that have received recent attention as a result of their persistence in the environment. Two analytical methods for the determination of perfluorinated surfactants in aqueous samples were developed in order to investigate a spill of 22000 L of fire retardant foam containing perfluorinated surfactants into Etobicoke Creek (Toronto, Ontario). With the first method, aliquots of surface water (0.2-200 mL) were preconcentrated using solid-phase extraction. Liquid chromatography/tandem mass spectrometry was employed for identification and quantification of each perfluorinated surfactant. Total perfluorinated surfactant concentrations in surface water samples ranged from 0.011 to 2270 microg/L, and perfluorooctanesulfonate was the predominant surfactant observed. Interestingly, perfluorooctanoate was detected in surface water sampled upstream of the spill. A second method employing 19F NMR was developed for the determination of total perfluorinated surfactant concentrations in aqueous samples (2-100 mL). By 19F NMR, the surface water concentrations ranged from nondetect (method detection limit, 10 microg/L for a 100-mL sample) to 17000 microg/L. These methods permit comprehensive evaluation of aqueous samples for the presence of perfluorinated surfactants and have applicability to other sample matrixes.

Journal Article↗

PubMed1996

Dopamine transporter binding in rat striatum and nucleus accumbens is unaltered following chronic changes in dopamine levels.

The effects of chronic treatment with the tyrosine hydroxylase inhibitor alpha-methyltyrosine or the dopamine precursor 1-3,4-dihydroxyphenylalanine on radioligand binding to the dopamine transporter in homogenates of rat striatum and nucleus accumbens were assessed. Chronic alpha-methyltyrosine administration decreased dopamine levels in both the striatum and nucleus accumbens without a resulting change in [3H]mazindol binding to the dopamine transporter in either brain region. In a second experiment, chronic administration of alpha-methyltyrosine or L-3,4-dihydroxyphenylalanine produced significant decreases and increases, respectively, in striatal dopamine levels without altering the binding of [3H]WIN 35,428, a chemically distinct dopamine transporter radioligand. These data suggest that even dramatic fluctuations in brain dopamine levels do not modulate the abundance of the dopamine transporter.

Animals↗

PubMed1995

Neurokinin-3 receptors modulate dopamine cell function and alter the effects of 6-hydroxydopamine.

Neurokinin-3 receptor expression within rat midbrain dopamine neurons was demonstrated using a combination of in situ hybridization and receptor autoradiographic techniques. Continuous intranigral infusion of the neurokinin-3 receptor agonist senktide selectively increased striatal dopamine metabolism over a period of several days, followed by apparent development of tolerance. In contrast, in animals with moderate unilateral 6-hydroxydopamine-induced lesions of nigrostriatal dopamine cells, intranigral senktide infusion increased dopamine turnover in the surviving dopamine neurons and reduced functional dopamine asymmetry (reflected by spontaneous rotations) over the 2-week period tested. Thus nigral neurokinin receptors can modulate normal dopamine cell activity and may provide a therapeutic target in the treatment of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Alterations in tyrosine hydroxylase expression following partial lesions of the nigrostriatal bundle.

Effects of destruction of central dopaminergic neurons on tyrosine hydroxylase gene expression were investigated. Two weeks after the unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, a 67% to 99% loss of striatal dopamine (DA) content was observed ipsilateral to the injection site. Measures of tyrosine hydroxylase (TH) protein levels revealed losses in striatal content proportional to DA content. Striatal dihydroxylphenylacetic acid (DOPAC) was somewhat less affected, resulting in 2- to 4-fold increases in the striatal DOPAC/DA ratio, depending on the severity of the lesion. Morphologically, surviving TH-positive substantia nigra pars compacta (SNc) neurons were more rounded than contralateral control cells, and exhibited decreases in cross-sectional area that were proportional to the loss of striatal DA. Measures of cytoplasmic TH mRNA levels in surviving neurons by in situ hybridization autoradiography revealed a significant 23% decrease in TH content per cell that could be correlated to lesion size. The decreases in cross-sectional area and TH mRNA content resulted in a small decrease in TH mRNA density of 6%. The determination of TH transcription rate by an intron-directed in situ hybridization assay found no significant change in TH transcriptional activity as a function of lesion. We conclude that the short-term effect of partial 6-OHDA-induced lesions of the nigrostriatal dopaminergic pathway is the selective loss or shrinkage of large DA neurons of the SNc, and that the associated down-regulation of TH mRNA expression in surviving neurons is due to a post-transcriptional mechanism related either to concomitant cellular hyperactivity or is secondary to the morphological alterations.

Animals↗

PubMed1995

Effects of intraoperative manual descending compressions on saphenous vein incision healing.

Many patients who undergo saphenous vein harvesting during aortocoronary bypass procedures experience saphenous vein incision site complications, such as hematoma formation. Twelve percent of the patients in this descriptive, comparative study developed hematomas in their saphenous vein incision sites. Contributing factors were age, smoking, diabetes, and intraoperative heparinization. An intraoperative nursing intervention (ie, manual descending compressions) did not decrease hematoma formation but warrants further investigation.

Adult↗

PubMed1994

The 5-HT1A agonist 8-OH-DPAT increases attachment maintenance but decreases suckling-related intake in 17-18-day-old rat pups.

Deprived and nondeprived preweanling (17-18 days of age) Sprague-Dawley rat pups were injected with 0, 0.03, 0.06, 0.1, or 0.5 mg/kg of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and observed in a suckling test using a milk replete anesthetized dam, with milk let-downs being intermittently precipitated via IV infusions of oxytocin. In experiment 1, the 0.5 mg/kg dose of 8-OH-DPAT was observed to increase the proportion of nondeprived animals which attached to a nipple; no dose effect was seen in deprived animals, who generally all attached. Deprived pups given the 0.5-mg/kg dose exhibited a lower frequency of nipple disattachment/reattachment following milk let-downs and had significantly lower percent body weight gains when compared with saline controls. In experiment 2a, the 0.5-mg/kg dose of 8-OH-DPAT was observed to decrease the overall incidence of nipple disattachment/reattachment as well as to suppress nipple shifting per se in both deprived and nondeprived 17-18-day-old rat pups; this dose also suppressed body weight gains in both the deprived and nondeprived pups. The suppression in weight gain by 8-OH-DPAT does not appear to be primarily related to a drug-induced reduction in nipple shifting. In experiment 2b, where pups were given access to only one nipple, an 8-OH-DPAT-related reduction in body weight gain was still evident. These experiments, which demonstrate that attachment maintenance and suckling ingestion are altered in opposite ways by 8-OH-DPAT, provide strong evidence that these two suckling-related phenomena are subject to different physiological controls.

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

PubMed1994

Cocaine exposure during pregnancy affects rat neonate and maternal brain glycosphingolipids.

Behavioral dysfunctions in offspring exposed in utero to cocaine have been observed, along with alterations in dopamine systems, but few studies of the underlying biochemistry have been conducted. Because of their documented roles in neuronal maturation, glycosphingolipids were analyzed in whole brains of offspring exposed gestationally to cocaine. Rat offspring exposed to cocaine in utero exhibited markedly elevated levels of both total gangliosides (p < 0.001) and neutral glycosphingolipids (p < 0.01) at postnatal day 1. However, by postnatal day 11 levels of gangliosides and neutral glycosphingolipids returned to control values. These effects were not restricted to chronic cocaine exposure early in life, in that ganglioside content of whole maternal brains was also elevated (p < 0.001), though less than that observed with the neonate brains. Qualitatively, no differences in ganglioside nor neutral glycolipid structure distribution were observed between cocaine-exposed and normal animals following separation by HPTLC and HPLC. These elevations are in contrast to those following alcohol exposure, where decreases in brain gangliosides have been observed. Neurochemical consequences of prenatal exposure to cocaine may be far-reaching and may not be restricted to the dopamine system.

Animals↗

PubMed1993

Effects of dopamine and kappa opioid receptors on fetal responsiveness to perioral stimuli.

Opioid ligands or drugs that act on dopaminergic pathways effect changes in the motor behavior of near-term rat fetuses. In this study, selective manipulation of kappa opioid and D1 DA receptors was used to investigate opioid and dopamine involvement in mediating the behavioral effects of milk infusion. Milk reduced expression of the fetal facial wiping response to a tactile probe, and this effect was blocked by the kappa antagonist nor-binaltorphimine as well as the D1 antagonist SCH-23390. Administration of either the kappa agonist U50,488 or the D1 agonist SKF-38393 mimicked the effects of milk and reduced fetal responsiveness to the probe in the absence of milk infusion. Administration of nor-binaltorphimine reversed the effects of SKF-38393 and resulted in a high incidence of the wiping response. However, administration of SCH-23390 did not reverse the low incidence of facial wiping induced by U50,488. These findings suggest that milk modulates activity at dopamine receptors, which in turn promotes activity at kappa receptors of the opioid system to bring about changes in cutaneous responsiveness in the fetal rat.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1993

Fetal behavior and the endogenous opioid system: D1 dopamine receptor interactions with the kappa opioid system.

Opioid or dopaminergic drugs can alter the motor behavior of rat fetuses on day 21 of gestation (E21). This study was conducted to a) characterize the behavioral effects of specific opioid agonists in the fetus, b) determine the effects of selective blockade of opioid receptors, and c) characterize the interaction between the dopamine and kappa opioid systems. Neither morphine nor the mu agonist DAMGO produced effects on fetal motor activity, whereas the kappa agonist U50,488 resulted in a pronounced increase in motor behavior. The selective antagonists beta-funaltrexamine (mu) and nor-binaltorphimine (kappa) produced no behavioral effects when administered alone. The D1 antagonist SCH-23390 did not reverse the activational effects produced by U50,488, but the kappa antagonist nor-binaltorphimine successfully blocked the increases in fetal behavior produced by the D1 agonist SKF-38393. These results are consistent with the hypothesis that activation of the dopamine system promotes activity at kappa opioid receptors to bring about changes in fetal motor activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1993

Fetal behavior and the dopamine system: activity effects of D1 and D2 receptor manipulations.

Binding studies have indicated that D1 and D2 dopamine receptor subtypes are present in rats before birth, but it is not known whether these receptors are functional during the prenatal period. In the present study, day-21 rat fetuses were prepared for direct observation after pharmacological manipulation of D1 and/or D2 receptors. The D1 agonist SK&F38393 induced a marked increase in fetal activity (i.e., forelimb, rearlimb, and head movements) while the D2 agonist quinpirole produced a slight suppression in activity. Coadministration of both agonists resulted in low levels of fetal activity, suggesting an interaction between D1 and D2 receptors. Administration of the D2 antagonist sulpiride resulted in little change in fetal behavior but was effective in blocking the behavioral activation induced by the D1 agonist. The D1 antagonist SCH23390, administered alone or in combination with the D2 antagonist, produced a modest increase in fetal activity that included mouthing and facial wiping behavior. These data provide evidence that the dopamine system is functional and capable of mediating behavioral effects in the near-term rat fetus. Further, manipulation of dopamine receptors results in a different pattern of behavioral effects than has been reported in older animals. The observation that fetal behavior is influenced by these pharmacological challenges suggests that drugs of abuse known to affect the dopamine system, such as cocaine, may cause profound changes in fetal behavior in utero that could consequently lead to alterations in behavioral and CNS development.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1992

Effects of acute dopamine depletion on responsiveness to D1 and D2 receptor agonists in infant and weanling rat pups.

The behavioral responses to separate and combined administration of the D1 agonist SKF-38393 and the D2 agonist quinpirole following acute dopamine (DA) depletion via alpha-methyl-p-tyrosine (AMPT) or AMPT/reserpine were examined in infant (10-day-old) and weanling (21-day-old) rat pups. At both ages, AMPT pretreatment generally had little impact on D1- or D2-agonist-induced responding, whereas the greater DA depletion observed following AMPT/reserpine pretreatment was generally associated with suppression of both D1 and D2-agonist-typical responding. Thus, whereas in adult animals some degree of D1 receptor activation by endogenous dopamine appears to be necessary for D2 responding but not vice versa (e.g. White et al. 1988), in young animals there appears to be a reciprocal co-dependence of these two receptor subtypes, with extensive DA depletion suppressing responding to both agonists when administered separately. At 10 days of age, some D1 and D2 agonist-induced behaviors that were previously blocked by AMPT/reserpine were reinstated following combined administration of both agonists. In contrast, no clear evidence for reinstatement was seen following administration of the combined agonists to AMPT/reserpine-pretreated weanlings, perhaps due to the induction of potential competing behaviors. Whereas DA depletion blocked many D1- and D2-induced behaviors, such depletion conversely promoted the expression in agonist-treated animals of a number of behaviors that were not normally induced by the agonists in non-depleted animals. These behaviors typically involved an oral component and included grooming and mouthing following SKF-38393 in depleted 10-day-old pups, mouthing following administration of either agonist to depleted weanlings, and probing and intense self-mutilation (forepaw and tongue biting) following the combined agonists in depleted weanlings. This rapid induction of potentiated agonist responsiveness following acute DA depletion early in life may have significant implications with regard to animal models for the developmental disorder of Lesch-Nyhan syndrome.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1992

Psychopharmacological responsiveness to the dopamine agonist quinpirole in normal weanlings and in weanling offspring exposed gestationally to cocaine.

The behavioral responsiveness to challenge doses of the D2 agonist quinpirole was examined in 21-day-old normal offspring (experiment 1) as well as offspring exposed gestationally to cocaine (experiment 2). In both experiments weanling rats received a subcutaneous injection of 0 (0.9% saline), 0.04, 0.08, 0.5, or 1.0 mg/kg/3 cc of the D2 agonist quinpirole and were placed in a divided glass testing apparatus containing either a dish of wet mash plus a food pellet or wood block (experiment 1) or both a food pellet and a wood block (experiment 2). Behaviors were recorded for 5 min via time-sampling at 30 and 60 min post-injection. In experiment 1 the three highest doses of quinpirole increased the amount of forward locomotion, rearing, sniffing and probing, as well as increasing directed oral movements at both the wood block and food pellet; in general these findings are reminiscent of those reported previously in adult animals. In experiment 2, cocaine-exposed weanlings exhibited an increased sensitivity to the stimulating effects of a low dose of the D2 agonist for forward locomotion and rearing as well as an increase in the overall incidence of sniffing behavior and chewing on food pellets. These data provide psychopharmacological evidence that the increase in striatal D2 binding previously observed in weanling offspring exposed gestationally to cocaine (Scalzo et al. 1990) may be associated with an increased behavioral sensitivity to the D2 agonist quinpirole.

Animals↗

PubMed1992

Ontogenetic differences in the psychopharmacological responses to separate and combined stimulation of D1 and D2 dopamine receptors during the neonatal to weanling age period.

The psychopharmacological responses to separate and combined stimulation of dopamine D1 and D2 receptors were examined in neonatal (postnatal day 3-4, P3-4), infant (P10-11) and weanling (P21-22) rat pups. Thirty minutes prior to testing rat pups received a subcutaneous (SC) injection of saline, 1.0 (P3-4, P10-11) or 0.5 (P21-22) mg/kg of the D2 agonist quinpirole. Fifteen minutes later all animals received an additional SC injection of 0, 0.01, 0.1, 1.0 or 10.0 mg/kg of the D1 agonist SKF-38393. Pups were tested for 5 min via a time-sampling procedure in a humidity controlled incubator for 3- and 10-day-old animals and in a divided glass aquarium for 21-day-old pups. Although administration of either agonist alone induced increases in forward locomotion and/or sniffing behavior at all test ages, the adult-typical grooming response to SKF-38393 and increase in vertical movements in response to quinpirole were not evident until weaning. Similarly, although combined administration of the agonists induced synergistic responding at each test age, only weanlings exhibited an adult-typical synergistic increase in licking. Thus, although the D1 and D2 receptor subtypes appear to be functionally present and coupled in some fashion throughout the neonatal to weanling age period, ontogenetic differences are evident in the behavioral responses elicited by separate and combined stimulation of these receptor subtypes.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1992

Prenatal cocaine exposure attenuates cocaine-induced odor preference in infant rats.

In order to further examine whether prenatal cocaine exposure alters the later reward efficacy of cocaine, exposed offspring were tested for cocaine-induced odor preference early in life. Test offspring were derived from Sprague-Dawley dams that received daily SC injections of 40 mg/kg/3 cc cocaine hydrochloride (C40) from gestational day 8-20, nutritional control dams receiving daily SC saline injections (NC), and nontreated control dams (LC). At testing on postnatal day 8 (P8), both LC and NC offspring were observed to exhibit a preference for the odor that had been paired on P7 with 2.0, 5.0, or 10.0 mg/kg cocaine. In contrast, C40 offspring exhibited a significant odor preference only when the odor had been previously paired with 5.0 or 10.0 mg/kg cocaine. These results, combined with previous work from our laboratory showing that adult offspring exposed gestationally to cocaine did not exhibit a cocaine-induced conditioned place preference, provide evidence that offspring exposed prenatally to cocaine are less likely to develop a preference for stimuli associated with cocaine. Further studies are needed to determine whether these alterations in cocaine preference reflect a learning deficit, pharmacokinetics factors, or an attenuation in the rewarding properties of cocaine.

Animals↗

PubMed1990

5-HT1A, 5-HT1B and 5-HT2 receptor agonists induce differential behavioral responses in preweanling rat pups.

Preweanling (postnatal day 17-18) Sprague-Dawley rat pups were tested in both the absence and presence of milk following administration of various doses of the 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) or ipsapirone, the 5-HT1B agonist 1-(3-chlorophenyl)piperazine (mCPP) or the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI). 8-OH-DPAT decreased mouthing while ipsapirone, mCPP and DOI had no effect upon this behavior. However, all four agonists significantly decreased grooming. Both 8-OH-DPAT and mCPP produced alterations in limb positioning, with 8-OH-DPAT administration resulting in a poor control of the hindlimbs and mCPP inducing a hindlimb straddle position. These functional responses to 5-HT1A, 5-HT1B and 5-HT2 agonists in preweanling pups vary from those observed previously in neonates. For instance, whereas inhibitory effects of 5-HT1A stimulation on mouthing are observed in both neonatal and preweanling pups, facilitory effects of 5-HT1B and 5-HT2 stimulation are only seen in neonates. These ontogenetic alterations may be related to the previously reported ontogenetic reversal in the effect of serotonergic activation upon mouthing and suckling that occurs during the neonatal to weanling age period.

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

PubMed1990

Cocaine facilitates prefrontal cortex self-stimulation.

It has been demonstrated that cocaine HCl lowers thresholds for and increases rates of medial forebrain bundle intracranial self-stimulation. The influence of cocaine on prefrontal cortex self-stimulation was assessed in the present experiment. The prefrontal cortex was chosen because evidence indicates that the neuroanatomical and pharmacological substrate for intracranial self-stimulation at this site may differ from the substrate for medial forebrain bundle self-stimulation. Cocaine significantly decreased train-duration thresholds and increased the rate of prefrontal cortex self-stimulation. It was concluded that cocaine facilitates both prefrontal cortex and medial forebrain bundle self-stimulation, perhaps by influencing neural activity in the mesocorticolimbic dopamine system. However, the role of dopamine in cocaine's effects at both sites remains speculative.

Animals↗

PubMed1990

Sensitization of rotation behavior in rats with unilateral 6-hydroxydopamine or kainic acid-induced striatal lesions.

Following unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra or unilateral kainic acid (KA) lesions of the striatum rats displayed rotation behavior in response to apomorphine (0.25 mg/kg SC or 1 mg/kg SC for the 6-OHDA- and KA-lesioned rats respectively). Three to five days following the initial apomorphine challenge rats were challenged under identical conditions with the same dose of apomorphine received previously. Both 6-OHDA- and KA-lesioned rats demonstrated a significant increase in the total number of rotations. Following a subsequent challenge with apomorphine, rats showed further increases in the total number of rotations. With the second and the subsequent apomorphine challenges there were significant increases in the maximal number of rotations, a significant decrease in the time of onset of rotation behavior and in some cases an increase in the duration of the rotation behavior. These increases in rotation behavior following repeated challenges with apomorphine indicate a supersensitivity to dopamine receptor agonists distinct from that elicited by lesions and chronic antagonist treatments. Furthermore, the utility of the rotation behavior model for testing the efficacy of dopaminergic agonists might be compromised if repeated challenges in individual animals are employed.

Animals↗

PubMed1989

Neurobehavioral teratogenicity of gestational cocaine exposure.

Gestational cocaine exposure has an impact on a number of behavioral and physiological measures examined during the neonatal to weaning age period. Notable effects of early cocaine exposure include a disruption in cognitive function, along with a profile of DA alterations. Observed physiological differences do not appear to be restricted, however, to the DA system, or even the nervous system. Such data may have important implications regarding the prognosis for future development of human offspring exposed gestationally to cocaine.

Animals↗