Seasat scanning multichannel microwave radiometer: results of the gulf of alaska workshop.

The scanning multichannel microwave radiometer results for the Gulf of Alaska Seasat Experiment Workshop are quite encouraging, especially in view of the immaturity of the data-processing algorithms. For open ocean, rain-free cells of highest-quality surface truth wind determinations exhibit standard deviations of 3 meters per second about a bias of 1.5 meters per second. The sea-surface temperature shows a standard deviation of approximately 1.5 degrees C about a bias of 3 degrees to 5 degrees C under a variety of changing meteorological conditions.

Superficial and juxtamedullary nephron function during saline loading in the dog.

A modification of the microdissection technique of Hanssen was utilized in dogs to measure superficial (SNGFR) and juxtamedullary nephron filtration rate (JMGFR) in control and saline-expanded dogs. During control studies SNGFR was 60+/-4 and JMGFR was 72+/-5 nl/min. During saline loading SNGFR was 74+/-8 and JMGFR was 65+/-6 nl/min. The ratio SNGFR: JMGFR significantly increased from 0.84+/-0.03 to 1.15+/-0.08. Glomerular perfusion rate (GPR) was measured with the microsphere method during control and saline loading. Superficial GPR did not change significantly but juxtamedullary GPR increased from 225+/-42 to 323+/-39 nl/min. Calculated superficial nephron filtration fraction was unchanged after saline expansion but juxtamedullary filtration fraction decreased from 0.34+/-0.07 to 0.24+/-0.07. The data demonstrate a tendency for filtration to shift toward the superficial part and plasma flow toward the deep part of the kidney cortex. GFR in juxtamedullary nephrons appears to be less plasma flow-dependent than in superficial nephrons. The fall in filtration fraction in the deep cortex may affect sodium excretion by juxtamedullary nephrons.

The role of endorphins in animal learning and behavior.

The present review examined the influence of endorphins in animal learning and behavior. It was suggested that in learning paradigms involving stress, the stressor elicits the release of endorphins. Given the evidence on endorphin-mediated, stress-induced analgesia, it was further suggested that the stress-induced release of endorphins modulates the aversiveness of the stressor, and as such, affects the learning based on this stressor. A number of learning paradigms, e.g., the conditioned emotional response, preference for signaled shock, conditioned taste aversions, and learned helplessness, were presented in support of this mediation of learning by the endorphins. A possible interaction between the endorphins and adrenocorticotropic hormone was offered as a physiological basis for this mediation.

Renal proximal tubular dysfunction and paroxysmal nocturnal hemoglobinuria.

A patient with paroxysmal nocturnal hemoglobinuria, who required many blood transfusions for hemolytic episodes, had a persistent hyperchloremic metabolic acidosis. Bicarbonate infusion demonstrated a large fractional excretion of bicarbonate (28.6 per cent at a plasma bicarbonate level of 23 meq/liter) which was consistent with proximal renal tubular acidosis. Generalized aminoaciduria and decreased tubular reabsorption of phosphate were also present. Marked deposition of iron in renal proximal tubules was associated with these functional abnormalities. We believe that, as systemic acidosis can promote hemolysis in patients with paroxysmal nocturnal hemoglobinuria, hemolysis can lead, by way of iron deposition in renal tubules, to further acidosis. This cycle should be interrupted with appropriate doses of bicarbonate.

Interagency coordination: the key to mainstreaming children with special needs into day care.

While the need for mainstreamed day-care services continues to increase, many barriers remain that prevent or delay providers from enrolling children with special needs. The suggestions in this article to coordinate local resources will help programs begin to provide initial necessary services to children with special needs. The use of volunteers will help supplement the staffing needs of a day-care center and allow for more individualized care of the children. Unfortunately, the absence of public funds for child day care continues to be a major barrier to creating appropriate programs for children with special needs. State and federal policies need to be expanded to support day care in general and children with special needs specifically. Part H of PL 99-457 (now Part H of IDEA PL102-119) is a national impetus to promote interagency collaboration at state and local levels. This is a beginning, but more state and federal funding is needed. In addition, regulations need to be developed that will make it easier rather than more difficult for local agencies to participate. Day-care providers and professionals in every community must work together to provide appropriate services to children with special needs. The most effective services use interdisciplinary teams to work together to plan and implement the care. Let us pick up the challenge of this mandate and develop programs that will help future generations recognize and accept the differences between individuals as well as see the similarities.

The interaction of cocaine and alcohol on schedule-controlled responding.

Within a number of physiological preparations, the effects of alcohol and cocaine in combination are reported to be greater than the effects of either drug given alone. Little has been reported, however, on the behavioral effects of the interaction. The present study investigated this issue by assessing the effects of cocaine and alcohol (alone and in combination) on schedule-controlled responding. Specifically, rats were trained to respond on an FR20 schedule for a water reinforcer. They were then administered cumulative doses of cocaine or alcohol. Following this, subjects were administered ineffective doses of alcohol prior to further dose-response assessments with cocaine and with ineffective doses of cocaine prior to further dose-response assessments with alcohol. Cocaine and alcohol alone produced dose-related decreases in responding. Furthermore, the dose-response function for cocaine was shifted to the left by alcohol and the dose-response function for alcohol was shifted to the left by cocaine. An isobolographic analysis revealed that the interaction between cocaine and alcohol was additive in nature. The possible bases for the interaction (e.g., changes in cocaine pharmacokinetics by alcohol and the formation of cocaethylene following co-administration of cocaine and alcohol) were discussed.

The interaction of cocaethylene and cocaine and of cocaethylene and alcohol on schedule-controlled responding in rats.

RATIONALE: Cocaethylene is a unique metabolite of cocaine, produced only in the presence of alcohol. This metabolite is pharmacologically, physiologically and behaviorally active. Further, it has been reported to interact pharmacokinetically with both cocaine and alcohol, an interaction that may mediate, in part, the interaction of cocaine and alcohol. Although cocaethylene has been shown to interact with both cocaine and alcohol, behavioral assessments of these interactions are limited. OBJECTIVES: To examine directly the behavioral interactions between cocaethylene and cocaine and between cocaethylene and alcohol, the present study assessed the effects produced by these combinations on schedule-controlled responding. METHODS: Rats were first administered cumulative doses of cocaethylene, cocaine and alcohol to assess their effects alone on responding. Following this, doses of cocaethylene were combined with cumulative doses of cocaine or alcohol. Additionally, doses of cocaine or alcohol were given in combination with cumulative doses of cocaethylene. RESULTS: When administered alone, cocaethylene, cocaine and alcohol produced dose-related decreases in responding. Further, cocaethylene shifted the dose-response functions for both cocaine and alcohol to the left and down, while cocaine and alcohol shifted the dose-response function for cocaethylene to the left and down. An isobolographic analysis revealed that these interactions were additive in nature. CONCLUSIONS: The present study suggests behavioral interactions between cocaethylene and cocaine and between cocaethylene and alcohol. The contribution of cocaethylene to the enhanced effects produced by the co-administration of cocaine and alcohol was discussed.

Cocaine-induced conditioned taste aversions: comparisons between effects in LEW/N and F344/N rat strains.

Recent studies have found the LEW/N rat self-administers drugs of abuse at higher rates than the F344/N rat, suggesting a genetic predisposition toward the abuse potential of drugs. The current study compared the acquisition of a conditioned taste aversion (CTA) to cocaine in these strains. During an initial 20-min daily session a 0.1% saccharin solution was available and a dose (0-50 mg/kg, SC) of cocaine was given immediately after that session. Water was available during sessions on the following 3 days. Fluid consumption was assessed over three saccharin/water cycles, and a final saccharin session. Vehicle injections (0 mg/kg) that followed exposure to saccharin had no effect on subsequent saccharin consumption. In contrast, when cocaine followed exposure to saccharin, rates of saccharin consumption decreased over successive saccharin sessions in a dose-related manner in both strains. The lowest dose (18 mg/kg) decreased consumption in LEW/N rats but not in F344/N rats. An intermediate dose (32 mg/kg) decreased consumption maximally in LEW/N rats and only marginally in F344/N rats. The highest dose (50 mg/kg) decreased consumption completely in LEW/N rats and almost completely in F344/N rats. These findings demonstrate that significant differences in sensitivity to stimuli paired with cocaine occur between these strains. These differences are consistent with previous reports that the LEW/N rat is uniquely sensitive to both behavioral and biochemical effects of drugs of abuse. The current report extends this sensitivity to the noxious effects of these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

The contribution of within-session averaging of drug- and vehicle-appropriate responding to the graded dose-response function in drug discrimination learning.

Prior work within the taste aversion baseline of drug discrimination learning has demonstrated that the generalization function for individual rats is graded in nature. In such work, intermediate doses of the training drug produced intermediate levels of drug-appropriate responding. Under some conditions, such graded responding has been reported to be due to an averaging of quantal drug- and vehicle-appropriate responding at different periods within the session. The present experiment assessed the contribution of such averaging to the graded responding within the aversion design. Rats were first trained to discriminate either 1mg/kg naloxone or 10mg/kg pentobarbital from distilled water. They were then administered various doses of the training drug (or a different drug), and the within-session pattern of licking was monitored minute by minute over the 20min session. Responding within the session was primarily either drug- or vehicle-appropriate. The specific pattern of drug- or vehicle-appropriate responding was presumably dependent upon the onset and/or offset of the drug stimulus. Thus, for the aversion baseline the graded response function for individual rats appears to be a function of the within session averaging of quantal (either drug- or vehicle-appropriate) responding.

A demonstration of the graded nature of the generalization function of drug discrimination learning within the conditioned taste aversion procedure.

Although control of discriminative performance will often generalize to different doses of the training drug or to drugs from the same class as the training drug, the nature of this generalization is unknown. Prior work has suggested that the generalization is primarily quantal in nature with animals displaying either vehicle-appropriate or drug-appropriate responding, depending upon their detection of the drug stimulus. It has been questioned whether this quantal nature of generalization reflects a characteristic response to drug stimuli or whether such responding is a function of the specific training and testing procedures used to establish and measure drug discrimination learning. The present paper evaluated this issue by analyzing the generalization functions of individual subjects trained and tested within one specific drug discrimination procedure, i.e. the conditioned taste aversion design. Responding within this design was generally graded. It is clear that quantal responding is not a necessary outcome of drug generalization assessments and that the nature of generalization in drug discrimination learning is a function of the specific procedure utilized in training and testing the discrimination. The results of the present analysis are discussed in terms of other recent work reporting graded functions.

The effects of trimethyltin chloride on the acquisition of long delay conditioned taste aversion learning in the rat.

Naive rats injected with LiCl at various times following consumption of a novel saccharin solution subsequently avoided the ingestion of saccharin with the degree of the aversion related to the interval between ingestion and LiCl administration. Although a similar relationship was also evident in animals which had received a single intragastric administration of trimethyltin chloride 21 days prior to the pairing of saccharin and LiCl, the trimethyltin-pretreated subjects receiving delayed injections of LiCl displayed weaker taste aversions than those not exposed to trimethyltin. This disruption in the acquisition of taste aversions over long delays is consistent with other work suggesting that trimethyltin disrupts tasks involving short-term memory. The utility of the conditioned taste aversion paradigm in detecting and characterizing drug toxicity was discussed.

A microcomputer-based system for stereotaxic coordinates in the rat brain.

In this report, the computer hardware and software used in the generation of a stereotaxic rat brain atlas are described. The atlas consists of sagittal and frontal sections drawn to the high-resolution page of the Apple II series computer. Brain architectural and macroscopic areas are represented by lines. Microscopic areas are represented by dots. The system employs a large data base to make available hundreds of brain areas on stereotaxic sections containing precise positional information of thousands of specific locations. For each display, the brain area is identified by name and by cross-hairs with digital display of stereotaxic coordinates. These coordinates may be referenced by earbar-zero or bregma. Other program options allow the printing of brain sections and a listing of available brain areas. Although designed for research in the neurosciences, the software may also be used for educational purposes.

Diminution of schedule-induced polydipsia after a long rest period.

Schedule-induced polydipsia was established in four food-deprived rats given daily hourly sessions in which a food pellet was presented once each min. Sessions were then discontinued for approximately six months. After this rest period, the daily sessions were resumed. Relative to the water intake during the last five sessions prior to the rest period, water intake during the first five sessions after the rest period exhibited a 55.5%, 10.3%, 32.0% and 29.6% decrement for the four rats, respectively. These results are discussed in terms of a sensitization view of schedule-induced polydipsia.

A software package for the microcomputer control and analysis of research on schedule-induced polydipsia.

This manuscript describes a software package called POLY which offers a range of routines designed to allow the user to set up, run and analyze data for research on schedule-induced polydipsia. The three major routines described are SETUP, RUN and ANALYSIS. The routines are flexible and give the user efficient control over the parameters of the research and the collection and analysis of the data. Although designed for research on schedule-induced polydipsia, the software can be used for other research purposes, requiring only changes in the support hardware.

Receptor mediation of the stimulus properties of cholecystokinin.

Recently, Melton, Kopman, and Riley (20) reported the rapid acquisition of drug discrimination learning using the sulfated form of cholecystokinin (CCK) within the conditioned taste aversion baseline of drug discrimination learning. The present study was designed to explore the receptor mediation of the stimulus properties of CCK within this procedure. Every fourth day, experimental subjects were given CCK-saccharin-LiCl pairings, and on the intervening recovery days, saccharin alone. Once discriminative control was established, doses of the CCK receptor antagonists devazepide (CCK-type A receptor subtype) and L-365,260 (CCK-type B receptor subtype) were administered in combination with the training dose of CCK. Unlike L-365,260 (1-1000 micrograms/kg), devazepide (1 microgram/kg) blocked the CCK stimulus, suggesting that within this design CCK's stimulus properties are mediated by the CCK-type A receptor subtype.

Buprenorphine as a stimulus in drug discrimination learning: an assessment of mu and kappa receptor activity.

Using the conditioned taste aversion baseline of drug discrimination learning, different groups of animals were trained to discriminate either buprenorphine or morphine from distilled water. Specifically, animals were injected with buprenorphine or morphine prior to a saccharin-LiCl pairing and the drug vehicle prior to saccharin alone. By the fifth conditioning trial, animals differentially consumed saccharin on the basis of administration of the drug or its vehicle. In subsequent generalization tests, buprenorphine stimulus control generalized completely to the mu agonist morphine in four of the five subjects tested, while morphine stimulus control completely generalized to buprenorphine in two of five subjects and partially generalized in the remaining three. Buprenorphine failed to generalize to the relatively selective kappa antagonist MR2266 and the broad-based antagonist diprenorphine. Morphine also failed to generalize to MR2266, but did generalize to diprenorphine. That morphine and buprenorphine displayed some degree of cross-generalization suggests that these compounds share some stimulus property, presumably their agonist activity at the mu receptor, and that the mu activity of these compounds was used in the establishment of the discrimination, a conclusion supported by the fact that compounds with mu antagonist activity (e.g., naloxone, MR2266) blocked both buprenorphine and morphine stimulus control. That buprenorphine failed to generalize to compounds with kappa antagonist activity suggests that animals trained to discriminate buprenorphine from its vehicle do not use the kappa antagonist activity of the drug in the establishment of the discrimination. The basis for the differential ability of various receptor subtypes to mediate the discriminative properties of compounds with mixed receptor activity was discussed.

Failure of cholecystokinin to precipitate withdrawal in morphine-treated rats.

In a test of the possible antagonistic interaction between cholecystokinin (CCK) and morphine, morphine-dependent rats were injected with one of three doses of CCK or with naloxone immediately following the consumption of a novel saccharin solution. Whereas opiate-dependent rats injected with the opiate antagonist naloxone acquired an aversion to the saccharin solution (and displayed a dramatic weight loss), CCK was without effect. These data were discussed in relation to the possible pharmacological antagonism between CCK and the opiates.

The differential effects of naloxone hydrochloride on the acquisition and maintenance of schedule-induced polydipsia.

Rats injected with the opiate antagonist, naloxone hydrochloride (10 mg/kg), 15 min prior to sessions in which they were given free food on a fixed time 75-sec schedule, displayed retarded acquisition of schedule-induced polydipsia relative to vehicle-injected subjects. Rats injected with naloxone after schedule-induced polydipsia had been acquired were unaffected, i.e., they continued to drink at control levels. Given that schedule-induced polydipsia has been considered non-opioid in nature, because of previous reports of its insensitivity to naloxone, the present report of differential effects of naloxone on the acquisition and maintenance of schedule-induced polydipsia suggests that some modification of this conclusion is necessary. Possible alternative mechanisms for these differential effects are discussed.

Cholecystokinin potentiates the rate-decreasing effects of morphine on schedule-controlled behavior in rats.

In one component of a multiple schedule, responding (licking in rats) was reinforced under a fixed-ratio (FR 50) schedule of water presentation. In the other component, responding had no programmed consequences (timeout). Each session consisted of four 10-min timeout components alternating with four FR components. In general, increasing cumulative doses of morphine (3.2-18 mg/kg) produced a dose-dependent decrease in the overall rate of responding. In one subject, cholecystokinin (CCK) alone (10-32 micrograms/kg) produced dose-dependent decreases in rate in the first component, while in the other two subjects relatively little decrease in rate occurred. When these doses of CCK were given as a pretreatment before morphine, the decrease in overall response rate was greater than that found with morphine alone. This interaction was most noticeable at the lowest dose of morphine where CCK produced a dose-dependent "potentiation" of the rate-decreasing effects. Although the potentiation of CCK was not as evident at the intermediate doses of morphine, there were instances in which the rate-decreasing effects produced by the combination were greater than those expected from addition of the effects of CCK and morphine alone. In contrast, when naltrexone (1 mg/kg) was given as a pretreatment, little or no rate-decreasing effects were produced by the cumulative doses of morphine. Furthermore, pretreatment with naltrexone and the administration of a higher dose range of morphine indicated the dose-effect curve for morphine had shifted approximately 3/4 log-units to the right.(ABSTRACT TRUNCATED AT 250 WORDS)

An assessment of the interaction between cholecystokinin and the opiates within a drug discrimination procedure.

Recently, cholecystokinin (CCK) has been reported to antagonize a variety of opiate-induced effects, including nociception, body shaking, thermoregulation, and locomotion. Consistent with these results, a number of CCK antagonists potentiate the opiates in a range of behavioral and physiological assessments. The present study further examined the interaction between CCK and the opiates within the conditioned taste aversion baseline of drug discrimination learning, a design that utilizes the stimulus properties of the drug to control consummatory behavior. Specifically, animals injected with CCK prior to saccharin-LiCl pairings and the CCK vehicle prior to saccharin alone rapidly acquired the CCK-vehicle discrimination, avoiding saccharin consumption following the administration of CCK and consuming the same saccharin solution following the vehicle. Although the stimulus properties of CCK did not generalize to either naloxone or diprenorphine, morphine blocked and naloxone potentiated CCK's stimulus effects. These data are thus consistent with a physiological (rather than a pharmacological) interaction between CCK and the opiates.