Biomedical subjects

M C Newland

Publications and source records attributed to M C Newland.

At least 19 recordsLinked to original sources

PubMed2004

Commissioning and operational experiences for the 160ML/d Woodman Point Sequencing Batch Reactor--control of settleability and denitrification using bioselectors.

Achieving and maintaining good biomass settling characteristics is a critical process design objective for any activated sludge wastewater treatment plant (WWTP), whether intermittent or continuous technology. One way of ensuring good sludge settleability in intermittent WWTPs is the incorporation of bioselectors in the process. A bioselector is essentially a small discrete reactor volume designed primarily for carbon absorption, in which activated sludge organisms are exposed to a high substrate concentration for a relatively short time. It is normally very much smaller than an anoxic zone and the activated sludge recycle is only a fraction of that typically adopted in continuous plants. With proper conditioning, recycled biomass rapidly absorbs and stores soluble organic wastewater components before transfer to the main treatment basin. This absorption and storage mechanism, and careful management of aeration throughout the intermittent treatment cycle, plays a crucial role in many subsequent growth and treatment processes, including sludge floc formation, denitrification and biological phosphorus removal. This paper examines some design considerations, and reviews the benefits of bioselectors by reference to the commissioning and initial operation of the new 160ML/d Woodman Point Sequencing Batch Reactor in Perth, Western Australia. The applicability of bioselectors in continuous plants is discussed.

Australia↗

PubMed2000

Animal studies of methylmercury and PCBs: what do they tell us about expected effects in humans?

Methylmercury and polychlorinated biphenyls (PCBs) exemplify the important interactions that should take place between epidemiological and laboratory investigations of developmental neurotoxicants. Often found in the same source, perhaps with multiplicative interactions, it is difficult to isolate specific profiles of effects without advanced behavioral procedures and controlled exposures using laboratory animals. The present review focuses on the effects of developmental exposure to methylmercury or PCBs as expressed in adult animals. The PCBs are subdivided into two structural classes, nonortho-substituted ("coplanar" or "dioxin-like") PCBs and ortho-substituted ("noncoplanar") PCBs, a distinction supported by different behavioral profiles and neural mechanisms of action. Methylmercury's profile is dominated by sensory effects with a likely cortical site of action. Some of these effects may be amplified with aging. Methylmercury's effects on functions generally termed cognitive can be understood by distinguishing between those reflecting the acquisition of a response-consequence relationship from those reflecting memory or contextual influences over behavior. Methylmercury does not appear to impair memory or discriminations, but retards acquisition of a response-reinforcer relationship. Like methylmercury, non-ortho-substituted PCBs do not appear to degrade memory and contextual control. Ortho-substituted PCBs impair performance on certain spatially-based discrimination and memory tasks. Methylmercury and non-ortho-substituted PCBs disturb the temporal pattern seen in fixed-interval schedules, but apparently without a significant change in the pattern of interresponse times. The ortho-substituted PCBs disrupted this pattern, but did so by increasing the number of short interresponse times.

Animals↗

PubMed1999

Blood and brain mercury levels after chronic gestational exposure to methylmercury in rats.

Female rats were exposed to 0, 0.5, or 6 ppm Hg (as methylmercuric chloride, 10 rats/group) in drinking water. For half the rats, exposure began 4 weeks before mating and for the others, exposure began 7 weeks before mating. All mating was done with an unexposed male. Maternal exposure continued to post-natal day (PN) 16. Blood and whole-brain mercury concentrations were determined in pups on PN 0 (birth) and PN 21 (weaning). Maternal water consumption was monitored daily during gestation and lactation. Maternal water consumption increased 2- to 3-fold through gestation for all groups. Mercury levels in blood and brain were unrelated to the duration of exposure before mating, although reproductive success appeared to be so related. Mercury levels in both media were closely related to consumption during gestation, but apparently maternal exposure during lactation did not result in exposure to the nursing pups. Brain mercury in offspring decreased between birth and weaning from 0.49 to 0.045 ppm in the low-dose rats and from 9.8 to 0.53 ppm in the high-dose rats. The brain increased in weight only about 5.5-fold during this time, indicating that there was minimal mercury exposure and some net loss from brain during this period. Brain:blood ratios averaged about 0.14 at birth and 0.24 at weaning, suggesting differential loss from neural and non-neural tissue. These ratios are higher than those reported in studies using less chronic exposure conditions or with adult rats. Brain concentrations of mercury in females in the low-dose group were about 10-15% higher than those seen in their male siblings. At the higher dose, the males had slightly higher levels of mercury in the brain than did their female siblings at birth. The relationship between brain concentration (in ppm) and cumulative mercury consumption, also expressed on a ppm basis (cumulative mercury consumed divided by maternal body weight at parturition), was not linear but was well described by a power-function relationship: Hg = A*(cum exposure)b where the exponent, b, was 1.12 and 1.17 for blood and brain, respectively, at birth. This exponent was indistinguishable from 1.0 for both media at weaning, indicating that the relationship between exposure and blood and brain levels became linear.

Animals↗

PubMed1998

Effect of once weekly treatment with 3,4-methylenedioxymethamphetamine on schedule-controlled behavior in rats.

The present study examined the effects of 3,4-methylenedioxymethamphetamine (MDMA), before and after once a week dosing, on the behavior of rats responding under a fixed ratio 20 schedule of reinforcement. Acutely, cumulative doses of MDMA dose-dependently decreased responding when compared to a series of water injections. Rats were then separated into two groups, one of which received only weekly MDMA ('paired') while the other received an additional injection of water each week ('unpaired'). Weekly dosing with MDMA resulted in significantly increased responding at low doses in the paired group but not in the unpaired group. When water injections were readministered there was a significant increase in responding in both groups. During the weekly regimen, locomotor activity also increased significantly over time after both water and MDMA injections. In conclusion, it appears that even weekly dosing with a small amount of MDMA can have long-lasting effects that are manifested in both operant and spontaneous behavior and that may be mediated by a conditioning mechanism.

Animals↗

PubMed1998

Discriminative and participant-rated effects of methylphenidate in children diagnosed with attention deficit hyperactivity disorder (ADHD).

Despite the demonstrated beneficial effects of methylphenidate and d-amphetamine for the treatment of attention-deficit hyperactivity disorder (ADHD), the discriminative and subjective effects of these compounds in children are not well understood. This study was designed to characterize such effects in children diagnosed with ADHD. In a series of 3 experiments, 17 children were examined to determine whether methylphenidate (n = 12) and d-amphetamine (n = 5) could be reliably discriminated at doses typically used in clinical practice. Under some conditions (e.g., when they were instructed to attend to the drug effects or when a wide range of doses was used), children discriminated methylphenidate (5.0-30.0 mg) from placebo. Children tested under a range of doses of d-amphetamine (2.5-20.0 mg) were unable to discriminate this drug from placebo reliably. Neither methylphenidate nor d-amphetamine produced reliable participant-rated effects.

Adolescent↗

PubMed1997

Quantifying the molecular structure of behavior: separate effects of caffeine, cocaine, and adenosine agonists on interresponse times and lever-press durations.

One difficulty in analyzing the molecular structure of behavior lies in reducing the data to a manageable size so that they can be described concisely but without a loss of important information. An approach to quantifying and comparing distributions of interresponse times (IRTs) and lever-press durations is described and then used to examine the acute effects of caffeine (an adenosine antagonist), cocaine, and three adenosine agonists in rats chronically consuming either tap water or water containing 1.0 mg/ml caffeine. The adenosine agonists used were R(-)N6-(2-phenylisopropyl)adenosine [R-PIA (preferential A1 receptor agonist)], 5'-(N-cyclopropyl)-carboxamidoadenosine [CPCA (preferential A2 agonist)], and 5'-N-ethylcarboxamidoadenosine [NECA (about equal agonist activity at A1 and A2 receptors)]. The rats' behavior was maintained under a Multiple Fixed-Interval (FI) 120 s, Duration > 5 s schedule of reinforcement. Under the FI schedule, the first lever-press after 120 s resulted in pellet delivery. Under the Duration > 5 s schedule, all lever-press durations greater than 5 s were reinforced. Molecular analyses of distributions of true IRTs (exclusive of lever-press durations) and lever-press durations were conducted by regressing percentiles of the distribution obtained from drug conditions against percentiles obtained from control conditions, a technique called empirical percentile-percentile analysis (or quantile-quantile analysis). The pattern of effects on response durations differed from that seen in IRTs. After acute administration of adenosine agonists, the distributions of lever-press durations under the FI schedule and subcriterion durations under the Duration > 5 s schedule were shifted rightward by a constant proportion, indicative of a generalized slowing of responding by these drugs. The effects of adenosine agonists on IRTs could be described by a power-function relationship whereby long IRTs were increased more than shorter ones. A rate-increasing dose of caffeine (10 mg/kg) did nothing to the molecular structure of lever-press durations or of IRTs, indicating that rate increases seen after this dose were due to an earlier onset of responding in the fixed-interval and were unaccompanied by disruptions in the physical execution of the response. The molecular structure of interresponse time distributions seen at the rate-decreasing dose of caffeine (60 mg/kg) resembled that of a rate-decreasing dose of cocaine, but not of the adenosine agonists. Both caffeine and cocaine produced a curvilinear relationship between drug and control percentiles such that very short IRTs were unaffected, but long ones were lengthened five- to 10-fold. This same dose of caffeine lengthened lever-press durations in a manner that resembled adenosine agonists but not cocaine. Percentile-percentile analyses reveal details about drug effects on the temporal structure of behavior and its physical execution that are not visible in molar analyses.

Adenosine↗

PubMed1997

Behavioral characterization of caffeine and adenosine agonists during chronic caffeine exposure.

Many of the behavioral actions of caffeine are mediated by its blockade of adenosine receptors, a notion that may have implications for tolerance and supersensitivity associated with chronic caffeine exposure. To examine possible interactions between chronic caffeine and adenosine-related actions of several drugs, the acute effects of caffeine and three adenosine agonists on behavior maintained by a Multiple Fixed-Interval (FI), Duration > 5 s schedule of reinforcement were studied using rats chronically consuming either 0 (tap water control), 0.5 mg/ml, or 1.0 mg/ml of caffeine in their drinking water. 5'-(N-cyclopropyl)-carboxamidoadenosine [CPCA (preferential A2 agonist)], 5'-N-ethylcarboxamidoadenosine [NECA (about equal agonist activity at A1 and A2 receptors)], and R(-)N6-(2-phenylisopropyl)adenosine [R-PIA (preferential A1 agonist)], as well as caffeine (nonspecific adenosine antagonist), were administered acutely i.p. after behavior stabilized. Dose-related decreases in overall response rate were produced by all adenosine agonists. Acute administration of all adenosine agonists and higher doses of caffeine increased average lever-press durations under the FI schedule from about 0.3 s to between 1 and 3 s, a three- to 10-fold increase. CPCA and NECA were 10 times more potent than R-PIA on all measures. Caffeine increased overall response rate under the FI schedule at doses of 3-30 mg/kg in nontolerant rats, and decreased rates at higher doses, which also increased lever-press durations. Insurmountable tolerance was seen to the rate-increasing effects of caffeine on behavior under the FI schedule, in rats exposed chronically to caffeine. Modest evidence of surmountable tolerance was seen in the rate-decreasing effects on the Duration > 5 s schedule. No tolerance to increases in lever-press durations or decreases in response rates was detected. Chronic exposure to caffeine did not alter the acute effects of the adenosine agonists: on all measures and with all adenosine agonists, the dose-effect curves for the three caffeine-exposure groups were indistinguishable from one another. The relative potencies suggest that the acute actions of adenosine agonists are related to A2 receptors. This is consistent with the failure to detect supersensitivity, since upregulation associated with chronic caffeine exposure appears primarily in A1 receptors.

Adenosine↗

PubMed1996

Behavioral consequences of in utero exposure to mercury vapor: alterations in lever-press durations and learning in squirrel monkeys.

Exposure to mercury vapor in utero results in the accumulation of mercury in the cerebellum, hippocampus, and other regions of the nervous system associated with motor function and learning, but little is known about the functional consequences of prenatal exposure. The offspring of pregnant squirrel monkeys exposed to 0.5 or 1.0 mg/m3 of mercury vapor during the last 2/3 or more of gestation were studied. Median maternal blood levels ranged from 0.025 to 0.18 microgram/g and exposures were estimated to range from 20 to 62 micrograms/day, with cumulative doses of 1304 to 4305 micrograms. Unexposed monkeys born at about the same time served as controls. The monkeys' lever pressing was maintained under various Concurrent Random-Interval Random-Interval schedules of reinforcement. Time allocation on each lever was examined during behavioral transitions and in steady state. No difference in sensitivity to reinforcer ratios was identified in steady state, but there was much more variability in the steady-state performance of exposed monkeys, as indicated by the standard deviation of the regression, than in controls. Logistic regression was used to examine the transition to new schedule parameters. Exposed monkeys were found to produce smaller or slower transitions than controls. The magnitude and stability of lever-press durations for controls and exposed monkeys were indistinguishable early in the experiment, but at the end the exposed monkeys had longer lever-press durations and the session-to-session variability was much greater. One monkey's exposure began during the third week of gestation (earlier than any of the others) and the behavior of this monkey was so erratic that some of the analyses could not be accomplished. Long-term effects of prenatal mercury vapor exposure included instability in lever-press durations and steady-state performance under concurrent schedules of reinforcement as well as aberrant transitions. The levels used were close to those reported in occupational settings under conditions of poor hygiene, but were at least 10- to 50-fold greater than those more commonly reported.

Administration, Inhalation↗

PubMed1994

Prolonged behavioral effects of in utero exposure to lead or methyl mercury: reduced sensitivity to changes in reinforcement contingencies during behavioral transitions and in steady state.

Postnatal exposure to lead or methyl mercury results in mental retardation, learning deficits, and other neurobehavioral effects in humans, and adverse consequences of prenatal exposure have been clearly documented with methyl mercury. To examine the developmental neurotoxicity of these metals, especially lead, concurrent schedules of food reinforcement were used to identify learning deficits in squirrel monkeys exposed during gestation to either methyl mercury or lead. Pregnant squirrel monkeys were administered methyl mercury (0.7 to 0.9 ppm in maternal blood) or lead (21 to 79 micrograms/dl in maternal blood) during the last half to two-thirds of gestation. At about 5-6 years of age, offspring were trained to lever press under concurrent schedules of reinforcement in which separate random interval reinforcement schedules operated independently on two levers. Reinforcement densities were varied such that 20 to 90% of the reinforcers were programmed to derive from the left lever (i.e., one lever was "richer" than the other). At steady state, the behavior of the controls was sensitive to reinforcement density and showed little lever bias, but the behavior of monkeys exposed to more than 40 micrograms/dl of lead and to methyl mercury was less sensitive to reinforcement rates and heavily biased. When relative reinforcement density on a lever changed, the unexposed animals' response rates gradually shifted to the newly rich lever. The behavior of monkeys exposed to methyl mercury or more than 40 micrograms/dl of lead changed slowly, not at all, or in the wrong direction. Steady-state behavior of monkeys exposed to less than 40 micrograms/dl resembled controls, but acquisition progressed more slowly and required 2-4 times as many reinforcers to complete. These effects suggest a behavioral mechanism--insensitivity to changing reinforcement contingencies--by which learning deficits and behavioral changes associated with these metals might be related to toxicant exposure. Since maternal blood levels corresponded to those that could be experienced in occupational settings, the present data raise the possibility of fetal hazards associated with maternal lead exposures at levels tolerated in humans in occupational settings.

Animals↗

PubMed1994

Behavioral and developmental effects of two 3,4-methylenedioxymethamphetamine (MDMA) derivatives.

The effects of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstacy') and two structurally related compounds, N-methyl-1-(3,4-methylenedioxyphenyl)-1-ethanamine (MDM1EA) and N-methyl-1-(3,4-methylenedioxyphenyl)-3-butanamine (HMDMA) were examined in two preparations: (i) a drug discrimination procedure in MDMA-trained rats and (ii) the chicken embryo, for determination of the direct effects of these compounds on the developing organism. The highest doses of MDM1EA and HMDMA partially substituted for MDMA, whereas higher (30-60 mg/kg) doses of HMDMA evoked clonic seizures in a separate group of rats. In chicken embryos MDMA had no effect on body, brain or liver weight, while the highest dose of MDM1EA decreased body weight and the 2 lowest doses of HMDMA increased body weight. All doses of HMDMA decreased liver weight (expressed as % body weight) when compared with contemporaneous water-treated controls. Taken together, the results of these experiments suggest that structurally related compounds share some stimulus properties with MDMA and may therefore share abuse liability. Furthermore, both MDMA-related compounds produced adverse effects on the developing organism, whereas MDMA did not.

3,4-Methylenedioxyamphetamine↗

PubMed1992

Persistent effects of manganese on effortful responding and their relationship to manganese accumulation in the primate globus pallidus.

Manganese produces signs and symptoms that suggest involvement of the basal ganglia, especially the globus pallidus and substantia nigra. Overt neurological signs have been reported in primates exposed to high levels of manganese (over 100 mg/kg) but little is known about the effects of lower doses. To examine these issues, three cebus monkeys were trained to operate a response device with their arms and legs by executing a rowing-like movement against a 3.9- to 4.1-kg spring through an arc length of 10 cm under a multiple fixed-ratio fixed-interval schedule of reinforcement. Over the course of 450 days, these monkeys were administered acute doses of 5 or 10 mg/kg iv of manganese chloride using a multiple baseline experimental design. Doses as low as 5 mg/kg provoked a large increase in the number of incomplete responses. The onset of manganese's effect appeared within days of exposure and developed over the course of several weeks. Its magnitude declined over the course of months, but after a cumulative dose of 10 to 40 mg/kg it did not return to baseline. Action tremor appeared at cumulative doses greater than 40 mg/kg and dystonia was never observed at the cumulative doses examined. Behavioral microanalysis revealed that manganese's effects initially appeared as increased variability of interresponse times and response duration. Later, the response pattern during the fixed ratio component shifted to one of progressively increasing durations through the course of the ratio. Magnetic resonance imaging revealed that the behavioral effects of manganese corresponded to an apparent increase in the manganese content of the globus pallidus and substantia nigra.

Animals↗

PubMed1992

Oral caffeine consumption by rats: the role of flavor history, concentration, concurrent food, and an adenosine agonist.

Some determinants of caffeine consumption by rats were examined using the two-bottle choice test. To describe the role of flavor history, groups of eight rats each received one of three fluids as their only source of fluid beginning at 29 days of age and continuing throughout the experiments. One group ("water") received tapwater, a second group ("caffeine") received 0.5 mg/ml caffeine in tapwater, and a third group ("quinine") received 0.01 mg/ml quinine in tapwater. Two-bottle choice tests began when rats were 40 days old. In the initial tests, caffeine rats drank more caffeinated water than water rats. Quinine rats were midway between these two groups. On a second block of tests, quinine and water rats' caffeine consumption increased so that the three groups were indistinguishable. When 0.5 mg/ml caffeine was available for 24 h, about one third of the total fluid consumption was of caffeinated water for all three groups. The presence of food greatly increased both caffeine and water consumption across a range of caffeine concentrations spanning 0.125-4.0 mg/ml. Increasing caffeine concentration generally increased consumption of plain water and decreased that of caffeinated water (but not total caffeine consumed) for water rats. Caffeine rats generally drank more caffeine than water rats, largely due to a tendency toward increased consumption of the 0.5-mg/ml concentration. Consumption of caffeinated water peaked at 0.5 mg/ml and showed graded decreases at higher and lower concentrations. Caffeine consumption showed dose-related increases with presession administration of l-phenylisopropyl adenosine. The serines of experiments characterize some of the determinants of caffeine consumption in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1992

Lecture practices in United States anesthesiology residencies.

We obtained data on lecture practices from 100 of the 110 university-affiliated anesthesiology residency programs certified in the United States in 1988. Of these residency programs, 36% had a majority of their lectures before the operating room schedule began, 57% had no lectures at all in this early time slot, and 78% had morning lectures at least once a week in conjunction with a delayed operating room start. Seventy-one percent of programs had one or more afternoon lectures each week. An attendance of more than 80% was reported in 66% of the programs for morning lectures and in 50% of the programs for afternoon lectures, which is a significant difference. Aggregate pass rates on the American Board of Anesthesiology written examinations in 1987 and 1988 correlated significantly with morning-lecture attendance, but not with afternoon-lecture attendance, number of lecture days per week, or mandatory lecture attendance. These findings suggest the need for further study and definition of the role of lectures in resident education in anesthesiology.

Anesthesiology↗

PubMed1992

Interactions between ethanol and pantothenic acid on tremor and behavior in squirrel monkeys.

Ethanol consumption alters the levels and distribution of pantothenic acid and its metabolic products, an effect that can be counteracted by preloading with pantothenic acid. Ethanol also produces significant disturbances in motor function and has a potent tremorolytic activity when administered acutely. To investigate the interaction of pantothenic acid and ethanol, the two substances were administered alone and in combination to three squirrel monkeys trained to perform a response-initiated positioning task that enabled the detection of tremor. Tremor was evaluated using spectral analytical techniques. Ethanol at 1.0 gm/kg produced a tenfold reduction in tremor over control sessions while pantothenic acid alone had no effect on tremor. Pantothenic acid (200 mg/kg, IP or IV) administered before ethanol intubation completely counteracted the tremor-reducing action of ethanol in two monkeys and partially counteracted it in a third. The interaction between pantothenic acid and ethanol was limited to these motor effects; the rate-reducing effect of ethanol was unaffected by pantothenic acid.

Animals↗

PubMed1992

Effects of self-generated rules on the development of schedule-controlled behavior.

College students responded under a multiple differential-reinforcement-of-low-rate 5-s fixed-ratio 8 schedule, with components alternating every 2 min. After 40 programmed minutes of acquisition and 12 min of maintenance, without notice, both schedules changed to extinction for 28 min. During acquisition, between alternations of the multiple schedule, some subjects were asked to develop rules describing the schedule contingencies. Other subjects were given these same rules between alternations, and a third group neither received nor were asked to develop rules. By the end of the acquisition phase, self-generated-rule subjects were more likely to show schedule-typical behavior than were subjects not asked to generate rules. The behavior of those given rules was similar to those asked to generate rules at the end of acquisition, but yoked-rule subjects acquired schedule-typical behavior at a quicker rate. By the end of extinction, during the period corresponding to the previous fixed-ratio interval, all no-rule subjects who had earned points during acquisition and maintenance were responding at a rate of less than 30 responses per minute. Only 3 of the 9 self-generated-rule subjects and 2 of the 5 yoked-rule subjects were similarly responding at this low rate. Results suggest that asking subjects to develop self-rules facilitates acquisition, but can retard extinction. Results also suggest that self-generated rules function similarly to external rules.

Adult↗

PubMed1991

Ethanol's effects on tremor and positioning in squirrel monkeys.

Ethanol ingestion markedly reduces tremor in patients with essential tremor. This clinical observation prompted the present experiments, which were designed to investigate ethanol's reduction of tremor in squirrel monkeys trained to execute a bar-holding task. A lever was attached to the hub of a rotary variable differential transformer (RVDT) and three squirrel monkeys were trained to position this lever within a 4.5 cm band for 8 seconds for a fruit juice reward. Behavior was maintained by a random ratio 2 schedule of reinforcement. Angular position of the lever was sampled for 5.12 seconds while the monkey held the bar, differentiated twice and analyzed to obtain a spectral description of tremor in units of acceleration 2/Hz. During control and vehicle sessions a spectral peak appeared at about 6-8 Hz and the magnitude of this peak varied from 25 to 150 milli-g2/Hz (where g is the acceleration due to gravity). A second peak appeared in two animals at greater than 15 Hz. For one animal this high-frequency peak was dominant during control sessions but the 6-8 Hz peak was dominant after intubation with water or ethanol. Ethanol produced consistent and dose-related decreases in the amplitude of the spectrum describing tremor but the location of the spectral peaks did not differ from vehicle sessions. The doses that altered tremor also produced an increase in the number of short-duration holds as well as other, less consistent, alterations in the form of the response. These data confirm and quantify ethanol's potency as a tremorolytic agent.

Alcohol Drinking↗

PubMed1990

Drug effects on an effortful operant: pentobarbital and amphetamine.

The behavioral effects of amphetamine and pentobarbital depend upon the conditions maintaining behavior. For example, amphetamine usually decreases the rate of operant behavior maintained by fixed ratio schedules while pentobarbital either increases it or leaves it unaffected. However, when considerable exertion is required, as in situations that require endurance, amphetamine tends to enhance performance while barbiturates degrade it. These differences complicate predictions of the effects of these two drugs on effortful operants. The present experiment was designed to characterize effortful responding behaviorally and pharmacologically. Cebus monkeys were trained to operate a lever by flexing their arms and extending their legs; this response exerted a force approximating their body weight. This operant was maintained by a multiple fixed ratio fixed interval (Mult FR FI) schedule. The two schedules maintained dramatically different response patterns. The FR schedule maintained vigorous, high rate responding characterized by a narrow IRT distribution centered at 0.5 sec. The FI schedule maintained very low overall rates of responding characterized by a variable IRT distribution with a median of 1.5 to 2 sec. Despite very low rates of responding during the FI component, no consistent rate increases appeared after amphetamine, and 0.3 mg/kg eliminated responding altogether. Pentobarbital increased overall rate but also shifted the interresponse time (IRT) distribution toward longer IRTs. The increase in overall rate arose from an earlier onset of responding during the FI component and occurred simultaneously with response slowing. The present studies do not support suggestions of a generalized enhancement of effortful performance by amphetamine or a generalized degradation by pentobarbital.

Animals↗

PubMed1989

Visualizing manganese in the primate basal ganglia with magnetic resonance imaging.

The paramagnetism of manganese was exploited to obtain proton nuclear magnetic resonance (MR) images of manganese-rich tissue in the central nervous system in vivo. One Macaca fascicularis monkey inhaled MnCl2 aerosol prior to imaging. A second M. fascicularis and two Cebus apellas were administered MnCl2 in various doses intravenously. The monkeys' brains were imaged before and after manganese administration in coronal and horizontal planes that included the basal ganglia and substantia nigra. A T1-weighted pulse sequence exploited manganese's reduction of spin-lattice relaxation times and clearly distinguished several separate and specific regions after manganese administration: the caudate nucleus, the lenticular nuclei, the substantia nigra, a region corresponding to subthalamic nucleus and ventromedial hypothalamus, and the pituitary gland. The kinetics of manganese accumulation were important in determining the imaged intensity of these regions but the route of parenteral administration was not. Spin-lattice relaxation times showed that T1 was shortened at lower doses of manganese and remained shortened longer in the globus pallidus and pituitary gland while little effect appeared in gray and white matter. T1 effects in caudate and putamen effects were intermediate. These data suggest selective affinity for manganese in globus pallidus and pituitary.

Animals↗