Commercial Hy-Line W-36 pullet and laying hen venous blood gas and chemistry profiles utilizing the portable i-STAT®1 analyzer.

Venous blood gas and chemistry reference ranges were determined for commercial Hy-Line W-36 pullets and laying hens utilizing the portable i-STAT®1 analyzer and CG8+ cartridges. A total of 632 samples were analyzed from birds between 4 and 110 wk of age. Reference ranges were established for pullets (4 to 15 wk), first cycle laying hens (20 to 68 wk), and second cycle (post molt) laying hens (70 to 110 wk) for the following traits: sodium (Na mmol/L), potassium (K mmol/L), ionized calcium (iCa mmol/L), glucose (Glu mg/dl), hematocrit (Hct% Packed Cell Volume [PCV]), pH, partial pressure carbon dioxide (PCO2 mm Hg), partial pressure oxygen (PO2 mm Hg), total concentration carbon dioxide (TCO2 mmol/L), bicarbonate (HCO3 mmol/L), base excess (BE mmol/L), oxygen saturation (sO2%), and hemoglobin (Hb g/dl). Data were analyzed using ANOVA to investigate the effect of production status as categorized by bird age. Trait relationships were evaluated by linear correlation and their spectral decomposition. All traits differed significantly among pullets and mature laying hens in both first and second lay cycles. Levels for K, iCa, Hct, pH, TCO2, HCO3, BE, sO2, and Hb differed significantly between first cycle and second cycle laying hens. Many venous blood gas and chemistry parameters were significantly correlated. The first 3 eigenvalues explained ∼2/3 of total variation. The first 2 principal components (PC) explained 51% of the total variation and indicated acid-balance and relationship between blood O2 and CO2. The third PC explained 16% of variation and seems to be related to blood iCa. Establishing reference ranges for pullet and laying hen blood gas and chemistry with the i-STAT®1 handheld unit provides a mechanism to further investigate pullet and layer physiology, evaluate metabolic disturbances, and may potentially serve as a means to select breeder candidates with optimal blood gas or chemistry levels on-farm.

Distributed communication and psychosocial performance in simulated space dwelling groups.

The present report describes the development and application of a distributed interactive multi-person simulation in a computer-generated planetary environment as an experimental test bed for modeling the human performance effects of variations in the types of communication modes available, and in the types of stress and incentive conditions underlying the completion of mission goals. The results demonstrated a high degree of interchangeability between communication modes(audio, text) when one mode was not available. Additionally, the addition of time pressure stress to complete tasks resulted in a reduction in performance effectiveness, and these performance reductions were ameliorated via the introduction of positive incentives contingent upon improved performances. The results obtained confirmed that cooperative and productive psychosocial interactions can be maintained between individually isolated and dispersed members of simulated spaceflight crews communicating and problem-solving effectively over extended time intervals without the benefit of one another's physical presence.

Perceptual and motor effects of morphine and buprenorphine in baboons.

The effects of morphine and buprenorphine on auditory perceptual discriminations and response latency ("reaction time") in baboons are compared. The task employed synthetic human vowel sounds that are readily generated in the laboratory, and closely approximate natural baboon "grunt" vocalizations [J. Acoust. Soc. Am. 101 (1997) 2951]. Baboons pressed a lever to produce one repeating "standard" vowel, and released the lever only when one of four other "comparison" vowels occasionally occurred in place of the standard vowel. The percentage of correct detections and median reaction time for each comparison were measured following intramuscular drug administrations of morphine (0.01-1.8 mg/kg) and buprenorphine (0.00032-0.032 mg/kg). Both morphine and buprenorphine impaired vowel discriminability, and greater impairments occurred for those comparison vowels that were more similar in formant structure to the standard vowel. Morphine increased reaction time in all baboons, and buprenorphine increased reaction time in two of three baboons. Morphine's perceptual effects occurred within 20-40 min following drug administration; buprenorphine's perceptual effects occurred 50-100 min following drug administration. Morphine and buprenorphine did not differ in the time course of their maximal reaction time effects. The results demonstrate that both morphine and buprenorphine can impair auditory discriminations involving human vowel sounds in baboons, as well as lengthen reaction times to the stimuli.

Effects of cocaine and quinpirole on perceptual and motor functions in baboons.

The effects of cocaine and quinpirole were studied in baboons to determine whether quinpirole, a relatively selective D2/D3 dopamine agonist, produced effects similar to those of cocaine on perceptual and motor processes. To measure perceptual and motor function, three baboons were trained to discriminate differences between a standard vowel and four other synthetic vowels: response accuracy as well as response latencies, or "reaction times", were measured following drug administrations. Cocaine reduced reaction times in two baboons, and did not affect reaction times in a third; on the other hand, quinpirole lengthened reaction times in a dose-dependent manner in all baboons. Cocaine and quinpirole also differed in the time course to produce the maximal reaction time effect following drug administration. Cocaine and quinpirole did not differ consistently in their perceptual effects, as indicated by similar changes in d', a signal-detection index of discriminability. These distinct profiles of effects for cocaine and quinpirole suggest differing neurochemical actions for these two drugs.

Patient retention in mobile and fixed-site methadone maintenance treatment.

The retention of patients (n = 399) enrolled in mobile health services (MHS), a Baltimore outpatient mobile methadone treatment program, was compared to patient retention (n = 1588) in six Baltimore fixed-site programs. Mobile program patients were retained for a median of 15.53 months in treatment in comparison to 3.90 for fixed-site patients (n = 664) from the MHS served zip codes (MHSZIPS) and 6.27 for fixed-site patients (n = 924) from zip codes other than those served by MHS (OTHERZIPS), (P < 0.001). Using Cox regression, the characteristics of patients associated with earlier discharge were (1) higher number of arrests, (2) more frequent cocaine use and (3) lower family income. These predictors of shorter retention were generally more prevalent among patients from the MHS served zip codes. Therefore, the longer retention in treatment of MHS patients as compared to OTHERZIPS fixed-site program patients is even more striking. Consistent with these differences in retention, were finding in a prior study suggesting that the mobile program provided greater access to services in reducing patient transportation cost and travel time. Thus, mobile methadone maintenance treatment appears to be a useful means of providing services.

Cocaine's effects on speech sound identification and reaction times in baboons.

The effects of cocaine on speech sound discriminations was examined to determine whether cocaine's previously demonstrated effect in reducing speech sound discriminability was dependent upon either the type of stimuli employed (simple tones versus complex speech) or the procedure (stimulus detection versus stimulus discrimination). Because of demonstrated similarities in the way that baboons and humans discriminate speech, and in the way the CNS is thought to encode and process speech sounds in these two species, baboons were trained to perform a choice procedure to identify the occurrence of different synthetic vowel sounds (see text). Animals held down a lever and released the lever only when one of four target vowels sounded, and not when a fifth, standard vowel sounded. Acute IM administration of cocaine (0.0032-1.0 mg/kg) produced dose-dependent decreases in vowel discriminability that were mostly due to elevations in false alarms (i.e., releases to the standard vowel) following cocaine. Cocaine also shortened reaction times to the stimuli in two of three baboons, but to a much lesser extent than observed previously. These results suggest that cocaine may interfere with the ability of the CNS to process the acoustic cues in speech sounds, and that the effects of cocaine on reaction times may depend upon the complexity of the reaction time procedure employed.

Cocaine's effects on speech sound discriminations and reaction times in baboons.

Three adult baboons were trained using a psychophysical procedure to discriminate between different synthetic vowel sounds [symbol: see text]. Baboons pressed and held a lever down to produce a pulsed train of a single reference vowel that served as the standard stimulus. Animals were trained to release the lever only when this standard vowel sound changed to one of the four remaining comparison vowels. A lever release within 1.5 s of this change in vowel sounds was defined as a correct detection of the change from the standard vowel to one of the comparison vowels, and was reinforced. All baboons readily learned the vowel discriminations and detected vowel changes at the 90-100% correct performance level. Acute IM administration of cocaine prior to test sessions (0.00032-3.2 mg/kg) produced dose-dependent decrements in vowel discriminability. At the same time, cocaine shortened lever release latencies (reaction times) to the vowel stimuli in two of three baboons. The cocaine-induced decrements in vowel discriminability were correlated with the degree to which frequency differences occurred among the different vowels in that lower vowel discriminability scores were found for those vowels with smaller spectral differences from the standard vowel. Further, false alarm rates were not systematically affected by cocaine, indicating that the cocaine-induced decrements in vowel discrimination accuracy occurred in the absence of systematic changes in the reliability of the baboons' discrimination performances.

Effects of cocaine on sensory motor function in baboons.

The effects of cocaine on auditory and visual threshold functions and reaction times were studied in baboons. Single IM injections of cocaine HCl (0.001-1.0 mg/kg) were administered once or twice weekly and were followed immediately by psychophysical tests designed to assess cocaine's effects on sensory thresholds and reaction times. Consistent reductions in reaction times were observed in the cocaine dose range of 0.032-0.32 mg/kg. Reaction times were decreased by 5-8% at the more effective cocaine doses. Concurrently measured auditory and visual threshold sensitivities showed no systematic changes at any of the cocaine doses studied.

Behavior analysis applications and interdisciplinary research strategies.

The emergence of behavioral pharmacology as a basic and applied science owes its origin and development to the interactive methodological-conceptual advances that have characterized interdisciplinary research initiatives over the past half century. The resulting enhancement of academic training and research opportunities has broadened the application of behavior analysis principles to a range of clinical, educational, and industrial settings. The extent of this applied behavioral science outreach is unconstrained even by the challenges of inhospitable terrestial and extraterrestial environments.

Acute ethanol effects on sensory/motor function in baboons with a history of chronic ethanol ingestion.

Baboons with a history of chronic, daily ethanol ingestion were subsequently studied under conditions that assessed the effects of acute oral self-administration of ethanol on auditory and visual threshold functions and reaction times. During the post-chronic experiment reported herein, the animals consumed specific amounts of ethanol twice weekly (0.1, 0.32, 1.0 or 1.3 g/kg), following which they immediately performed psychophysical tests designed to assess ethanol's effects on sensory thresholds and reaction times. Clear, dose-related increases in reaction times were observed following ethanol doses greater than 0.32 g/kg. Trends within individual threshold functions were consistent with systematic changes in auditory and visual threshold sensitivities of 1-3 dB at the high ethanol doses. Reaction time increases ranged from 25 to 180 ms above baseline levels at the highest dose (a 15% average increase). These general findings however, were in contrast to data obtained in the same animals under conditions of daily, chronic ethanol administration which characteristically showed greater sensory/motor effects of up to twice the magnitude of those observed with single doses.

Zolpidem behavioral pharmacology in baboons: self-injection, discrimination, tolerance and withdrawal.

This study examined in baboons various behavioral effects of zolpidem, a short-acting imidazopyridine hypnotic which has selectivity for subtypes of the benzodiazepine receptor. Intravenous drug self-injection was studied under a fixed-ratio 80- or 160-response schedule with a 3-hr timeout after each injection. Maximal rates of self-injection maintained by zolpidem (0.01-1 mg/kg) were consistently higher than those maintained by vehicle and the benzodiazepine hypnotic triazolam. Substitution of vehicle after about 2 weeks of zolpidem self-injection (7-8 mg/kg/day) resulted in a time-limited suppression of food pellet intake, indicating a drug withdrawal effect. In a drug discrimination study, baboons were trained to discriminate either lorazepam (1.8 mg/kg p.o.) or pentobarbital (10 mg/kg p.o.) from the no-drug condition. Zolpidem (0.1-18 mg/kg p.o.) occasioned both lorazepam- and pentobarbital-appropriate responding (greater than 80%) in a dose-dependent manner. In a final experiment, zolpidem (3.2 or 5.6 mg/kg i.m.) produced ataxia and sedation that progressively decreased over 7 consecutive days of administration. The withdrawal, discriminative stimulus effects and tolerance shown with zolpidem were similar to those shown previously with benzodiazepines under similar conditions. The rates of self-injection of zolpidem were similar to those maintained by intermediate duration barbiturates (e.g., pentobarbital) and higher than those maintained by 11 benzodiazepines studied previously under similar conditions. Further research on the reinforcing effects of zolpidem may provide useful insights into mechanisms underlying the maintenance of behavior by compounds acting through the benzodiazepine receptor.

Acute opioid administration effects on sensory and motor function in baboons: buprenorphine, morphine, and naloxone.

The effects of acute administration of the opioid compounds buprenorphine, morphine, and naloxone were studied on auditory and visual threshold functions and reaction time performances in baboons. Baboons were trained in a reaction time procedure to hold a lever depressed, and release the lever when a signal was presented. Auditory and visual signals were employed in separate sessions. Drug was administered 30min prior to testing. Dose-related increases in visual and auditory thresholds were observed following buprenorphine, with visual thresholds being somewhat more drug-sensitive. Buprenorphine also increased reaction times to both high-intensity and low-intensity stimuli. High doses of morphine increased reaction times to high-intensity auditory and low-intensity visual stimuli; thresholds for both modalities were unaffected by any dose of morphine. Naloxone produced no consistent effects on thresholds or reaction times. False alarm rates were not significantly changed by buprenorphine, morphine, or naloxone.

Response patterns and cardiovascular effects during response sequence acquisition by humans.

The effects of temporal delays imposed between successive responses and of vitamin C administration were examined on the acquisition of response sequences and on cardiovascular reactivity during sequence acquisition. Thirteen adult subjects (6 female, 7 male), in good health, gave written consent prior to participating in 12 weekly 45-min sessions. Points, exchanged for money after each session, were presented when subjects completed 15-response sequences on a touch-sensitive three-response keypad. A position counter increased from 0 to 14 as subjects emitted correct responses in the sequence. Four novel 15-response sequences were presented each session. No delays were imposed between successive responses during the acquisition of one sequence; delays were imposed immediately following each response during the acquisition of a second sequence, thereby delaying response feedback; delays were imposed following feedback during acquisition of a third sequence, resulting in the removal of the stimulus correlated with sequence position; and, as a control condition, delays were imposed following feedback, but stimuli correlated with sequence position were reinstated prior to the next response during acquisition of a fourth sequence. Subjects were exposed to one of two delay durations (0.2 and 0.5 or 0.5 and 1.0 s) each session, and delay durations alternated every session. During Weeks 5 to 8, subjects received 3 grams of vitamin C per day, whereas during Weeks 1 to 4 and 9 to 12, subjects received placebo under single-blind conditions. All subjects acquired the sequences, as evidenced by decreasing percentages of incorrect responses across trials. When temporal delays were imposed between successive responses during sequence acquisition, acquisition efficiency was enhanced. Examination of response latencies suggested that the status of preceding responses (i.e., correct or incorrect) rather than the status of the position counter influenced subsequent responding. Cardiovascular effects were inversely related to the length of the temporal delay. Neither cardiovascular reactivity or sequence acquisition were related to vitamin C administration.

Rat AA-26: behavioral pharmacology science pioneer.

Rat AA-26, despite 1950s "state of the art," nonetheless generated the first set of behavioral pharmacology cumulative records to appear in the weekly journal Science, the century-old publication of the American Association for the Advancement of Science. The laboratory exploits of this dedicated animal called early attention to the methodological fruits of a marriage between pharmacology and the experimental analysis of behavior.

Self-injection of barbiturates, benzodiazepines and other sedative-anxiolytics in baboons.

Self-injection of 12 sedative-anxiolytics was examined in baboons. Intravenous injections and initiation of a 3-h time-out were dependent upon completion of a fixed-ratio schedule requirement, permitting eight injections per day. Before testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. At some doses, all five of the benzodiazepines examined (alprazolam, bromazepam, chlordiazepoxide, lorazepam, triazolam) maintained rates (number of injections per day) of drug self-injection above vehicle control in each of the baboons tested. Maximum rates of benzodiazepine self-injection were generally submaximal. Of the benzodiazepines examined, triazolam maintained the highest rates of self-injection. Among the three barbiturates tested, methohexital generally maintained high rates of self-injection in contrast to hexobarbital and phenobarbital, which only maintained low rates. Of the four non-benzodiazepine non-barbiturate sedatives examined, both chloral hydrate and methyprylon occasionally maintained high rates of self-injection. Although there were differences within and across animals, baclofen maintained intermediate rates of self-injection. The novel anxiolytic buspirone maintained only low rates of self-injection that were not different from vehicle. This study further validates the self-injection methodology for assessing sedative-anxiolytic abuse liability and provides new information about drug elimination rate as a determinant of drug self-administration.

Animal models for assessing drugs of abuse.

A major toxic effect that has limited the clinical usefulness of medicinal drugs has been their susceptibility to nonmedical use and abuse by significant segments of the population. Major research efforts have been directed toward the development of safer and more effective therapeutic agents that would not be subject to such misuse, and laboratory animal assessment models have contributed importantly to the evaluation of such compounds. There are now several converging lines of evidence that testify to the reliability and broad generality of observations concerning drug abuse liability in humans based upon such animal laboratory models. The most important point of contact that characterizes the interaction between such animal assessment models and the human drug abuse arena is the demonstrated relationship between the biochemical/pharmacological/toxic properties of drugs on the one hand, and their environmental/behavioral stimulus functions on the other. As a result of these developments in animal model research technology and the consequent advances in knowledge of drug action, an operational basis has been provided for redefining the bewildering range of phenomena and experiential pseudo-phenomena loosely identify with such terms as "addition," "dependence" and "abuse."