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.

Preavoidance blood pressure elevations accompanied by heart rate decreses in the dog.

Blood pressure and heart rate were monitored continuously in five dogs for 1 hour before performance on a free-operant shock-avoidance task. Cardiovascular changes during the preavoidance hour were characterized by sustained and significant increases in blood pressure, and sustained and significant decreases in heart rate.

Instrumental conditioning of large-magnitude, daily, 12-hour blood pressure elevations in the baboon.

Blood pressure and heart rate were monitored continuously in four baboons during extended exposure to a daily 12-hour conditioning procedure providing food and shock-avoidance as contingent consequences of prespecified increases in diastolic blood pressure. Sustained and significant increases (30 to 40 mm-Hg) in both systolic and diastolic blood pressure were maintained throughout the daily 12-hour conditioning sessions, accompanied by elevated heart rates.

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.

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."

Relative abuse liability of triazolam: experimental assessment in animals and humans.

The abuse liability of a drug is a positive, interactive function of the reinforcing and adverse effects of the drug. The relative abuse liability of the hypnotic benzodiazepine, triazolam, has been controversial. This paper reviews animal and human studies bearing on its relative abuse liability, including data on pharmacological profile, reinforcing effects, liking, speed of onset, discriminative stimulus effects, subjective effects, physiological dependence, rebound and early morning insomnia, drug produced anxiety, lethality in overdose, psychomotor impairment, interactions with ethanol, anterograde amnesia, impaired awareness of drug effect, and other psychiatric and behavioral disturbances. It is concluded that the abuse liability of triazolam is less than that of the intermediate duration barbiturates such as pentobarbital. Although there are considerable data indicating similarities of triazolam to other benzodiazepines, there is also substantial speculation among clinical investigators and some limited data suggesting that the abuse liability of triazolam is greater than that of a variety of other benzodiazepines, and virtually no credible data or speculation that it is less. Further research will be necessary to clarify definitively the abuse liability of triazolam relative to other benzodiazepines.

Relationship between anorectic and reinforcing properties of appetite suppressant drugs: implications for assessment of abuse liability.

A quantitative ratio measure was developed which permitted comparisons between the reinforcing and anorectic potency of eight phenylethylamine anorectics and cocaine in laboratory baboons. The ordering of these compounds based upon this ratio bears a reasonable correspondence to clinical drug evaluations. The measure may provide information for preclinical evaluation of relative abuse potential of anorectic drugs.

Diazepam and delta-9-THC: contrasting effects on the discrimination of speech sounds in nonhuman primates.

The adult male baboons were trained on a psychophysical procedure to discriminate five synthetic, steady-state vowel sounds (/a/, /ae/, /e/, /U/, and /c/) from one another. A pulsed train of one vowel comprised the reference stimulus during a session. Animals were trained to press a lever and release the lever only when this reference vowel sound changed to one of the comparison vowels. All animals learned the vowel discriminations rapidly and, once learned, performed the discriminations at the 95-100% correct level. The IM administration of diazepam (0.32, 1.0, 3.2, and 10.0 mg/kg) produced dose-dependent decrements in vowel discriminability. The diazepam-induced decrements in vowel discriminability were correlated with the degree of spectral frequency differences found among the different vowels, with lower vowel discriminability scores found for those vowels with smaller spectral differences from the reference vowel. In contrast, oral administration of delta-9-THC (0.32, 1.0, 3.2, and 5.6 mg/kg) produced no decrements in vowel discriminability.

Effects of d-methamphetamine on auditory and visual reaction times and detection thresholds in the baboon.

Baboons were trained in both auditory and visual reaction time procedures to release a response lever in the presence of low-intensity stimuli. By varying the stimulus intensity from trial to trial, functions relating reaction time (elapsed time from stimulus onset to lever release) to stimulus intensity were established, and detection thresholds were measured. The effects of acute, IM injections of d-methamphetamine (0.001-1.0 mg/kg) were examined on these psychophysical performance baselines. Reaction times for acoustic stimuli generally were faster for higher drug doses, whereas reaction times for visual stimuli either lengthened or shortened, depending on both drug dose and individual differences among animals. Auditory thresholds were unaffected at all drug doses studied, whereas visual thresholds were generally elevated at doses of 0.1 mg/kg and above.

Progressive ratio and fixed ratio schedules of cocaine-maintained responding in baboons.

Responding maintained under progressive ratio (PR) and fixed ratio (FR 160) schedules of IV saline or cocaine (0.01-4.0 mg/kg) injections was studied in baboons. Each injection was followed by a time-out period which was 3-h with the PR schedule and was either 3 or 12 with the FR schedule. On the PR schedule the ratio requirement was systematically increased each day until reaching the 'breaking point' at which self-injection performance fell below a criterion level (one or zero injections per day). Overall response rates on the PR schedule increased with progressive increases in the ratio until a maximum at which an abrupt reduction in responding occurred. With the 3-h time-out the dose-breaking point function on the PR schedule was similar to the dose-response rate function on the FR schedule. These dose-effect functions were inverted U-shaped curves characterized by a graded ascending limb (0.01-0.32 mg/kg) and a downturn at the highest doses (3.0-4.0 mg/kg). On the FR schedule the downturn in the dose-response rate function was attributable to a cumulative drug effect as revealed by manipulation of time-out duration and analysis of sequential interresponse time distributions and cumulative response records. PR and FR schedules provide similar information about the relative reinforcing efficacy of different cocaine doses.

Effects of diazepam and triazolam on auditory and visual thresholds and reaction times in the baboon.

Adult male baboons were trained on a psychophysical procedure that measured detection thresholds and reaction times for pure tone and white light stimuli. Intramuscular injections of diazepam or triazolam were given 30 min before session onset; stimulus intensity was randomly varied from trial to trial, and four to five estimates of sensory thresholds and reaction times were obtained throughout each session. Diazepam produced dose-related elevations of both auditory and visual thresholds and reaction times. Effects of a single high dose of diazepam were apparent 4-5 days after administration. Triazolam was approximately 100 times more potent than diazepam in elevating reaction times and visual thresholds, but did not elevate auditory thresholds. There were no residual effects of triazolam on the day after dosing. These results suggest that diazepam and triazolam produce qualitatively similar effects on basic psychophysical function, but that they can be differentiated on the basis of sensory modality changes and post-drug recovery time.

Comparison of behavior maintained by infusions of eight phenylethylamines in baboons.

Doses of eight phenylethylamines were substituted for cocaine on a drug-maintained behavior baseline in baboons. Intravenous infusions of drug were contingent upon completion of 160 lever presses (a 160-response fixed-ratio schedule; FR 160). A 3-h time-out period followed each infusion, permitting a maximum of 8 infusions per day. Fenfluramine was the only drug that did not maintain self-infusion performance at any dose tested. d-Amphetamine was approximately 10 times more potent than phentermine, phenmetrazine or diethylpropion, and 20 to 30 times more potent than methylenedioxyamphetamine (MDA), clortermine or chlorphentermine, in maintaining self-infusion behavior. Some doses of d-amphetamine and phentermine produced a cyclic pattern of drug intake over days. Increasing self-infused doses of all drugs produced a substantial suppression of concurrent food-maintained behavior. There was no clear relation between the potency of the phenylethylamines in maintaining self-infusion performance and the potency in suppressing food-maintained behavior which indicates that different mechanisms may underlie the two effects. Examination of chemical structures indicates that substitution on the phenyl ring may decrease the potency of phenylethylamines in maintaining self-infusion behavior.

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.

Phencyclidine-analogue self-injection by the baboon.

Self-injection of phencyclidine HCI (PCP) and four of its analogues was examined in baboons. IV injections of drug were dependent upon completion of 160 lever presses (a 160-response fixed-ratio schedule). A 3-h time-out period followed each injection, permitting a maximum of eight injections per day. Self-injection performance was first established with cocaine and, once stable, test doses of each drug were substituted for 15 days. All five compounds maintained maximal self-injection performance, differing only in their relative potencies. The order of potency was approximately PCP greater than NMPCA = TCPY greater than NNBPCA greater than ketamine. Analysis of the distribution of injections throughout the day indicate that lower doses (and vehicle) were injected mainly during the daylight hours (i.e., 9 AM-6 PM), but as the dose was increased the injections became more uniformly distributed. Only the highest doses of these compounds affected food intake, though the degree of suppression was modest. No differences between these compounds with respect to their abuse potential could be found.

Self-injection of barbiturates and benzodiazepines in baboons.

Self-injection of three barbiturates, six benzodiazepines, and chlorpromazine was examined in baboons. Intravenous injections of drug were dependent upon completion of 160 lever presses (a 160-response fixed-ratio schedule). A 3-h time-out period followed each injection, permitting a maximum of eight injections per day. Prior to testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. Amobarbital, pentobarbital, and secobarbital maintained the highest levels of self-injection, which were similar to those maintained by cocaine. Clonazepam, clorazepate, diazepam, flurazepam, medazepam, and midazolam maintained relatively modest levels of self-injection, while chlorpromazine maintained only low levels, which were in the range of vehicle control. Of the six benzodiazepines, midazolam produced the highest levels of self-injection. At the highest self-injected doses, the barbiturates produced anesthesia in contrast to the benzodiazepines, which produced only sedation. None of the drugs affected food intake except for chlorpromazine, which produced dose-related decreases. The differences among the drug classes (i.e., barbiturate, benzodiazepine, phenothiazine) with respect to the maintenance of self-injection correspond well with the results of previous animal and human drug self-administration studies.

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.

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.

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.

Effects of marijuana on the task-elicited physiological response.

Ten healthy male marijuana users smoked either a placebo or active (1.8% delta 9-THC) marijuana cigarette during five daily testing sessions. Ten minutes after drug administration, six subjects (Group I) performed a 10-min serial acquisition task and four subjects (Group II) rested quietly. Blood pressure was sampled at 2-min intervals and heart rate (HR) was recorded continuously. Marijuana alone increased HR by 18 beats/min and mean arterial pressure (MAP) by 3 mmHg, while task performance alone increased HR by 4 beats/min and MAP by 5 mmHg. The combination of drug and task performance had greater cardiovascular effects than either task performance or marijuana alone, with HR increased by 29 beats/min and MAP increased by 15 mmHg. These results suggest that marijuana smoking may increase cardiovascular responsivity.