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Biomedical subjects

E J Mazurski

Publications and source records attributed to E J Mazurski.

15 recordsLinked to original sources

Effect of peer led programme for asthma education in adolescents: cluster randomised controlled trial.

OBJECTIVE: To determine the effect of a peer led programme for asthma education on quality of life and related morbidity in adolescents with asthma. DESIGN: Cluster randomised controlled trial. SETTING: Six high schools in rural Australia. PARTICIPANTS: 272 students with recent wheeze, recruited from a cohort of 1515 students from two school years (mean age 12.5 and 15.5 years); 251 (92.3%) completed the study. INTERVENTION: A structured education programme for peers comprising three steps (the "Triple A Program"). MAIN OUTCOME MEASURES: Quality of life, school absenteeism, asthma attacks, and lung function. RESULTS: When adjusted for year and sex, mean total quality of life scores showed significant improvement in the intervention than control group. Clinically important improvement in quality of life (>0.5 units) occurred in 25% of students with asthma in the intervention group compared with 12% in the control group (P=0.01). The number needed to treat was 8 (95% confidence interval 4.5 to 35.7). The effect of the intervention was greatest in students in year 10 and in females. Significant improvements occurred in the activities domain (41% v 28%) and in the emotions domain (39% v 19%) in males in the intervention group. School absenteeism significantly decreased in the intervention group only. Asthma attacks at school increased in the control group only. CONCLUSION: The triple A programme leads to a clinically relevant improvement in quality of life and related morbidity in students with asthma. Wider dissemination of this programme in schools could play an important part in reducing the burden of asthma in adolescents.

Absenteeism↗

Second generation effects of maternal alcohol consumption during pregnancy in rats.

1. Previous studies have shown that when female rats are administered alcohol during pregnancy there are adverse effects on their progeny, including decreased birth weight and delayed neuromotor development. Evidence from several sources suggests alcohol exposure may contribute to cytogenetic abnormalities, suggesting the possibility of cross generational effects from prenatal exposure. 2. On day 1 of gestation female rats were randomly allocated to the Alcohol group, which received a liquid diet containing 5% (v/v) ethanol solution until parturition, the Sucrose control group, which received an identical diet, except that sucrose had been isocalorically substituted for ethanol, or the Chow control, which received standard laboratory chow. 3. When the offspring of these rats reached adulthood they were mated with drug-free rats and the development of their offspring was monitored. 4. In comparison with female pups whose sires had been exposed to alcohol in utero, the weight of pups descended from fetally-exposed dams increased more slowly from day 1 to day 7. 5. At five days of age, significant differences favouring the two control groups were found in latency to right for pups descended from fetally-exposed dams. 6. These data suggest that the effects of prenatal exposure to alcohol are more pervasive than previously thought and affect female pups to a greater extent than males.

Alcohol Drinking↗

Covariation bias for phylogenetic versus ontogenetic fear-relevant stimuli.

In the present study, two groups of 21 subjects with either high or low fear of both snakes (or spiders) and damaged electrical outlets/appliances participated in a two phase experiment. After reading a description of an illusory correlation experiment, subjects were asked to imagine themselves participating in it. They rated their expectations for the number of occasions on which slides of snakes, electrical outlets, and flowers would be followed by either a shock, tone, or nothing. As predicted, both high and low-fear subjects reported an expectancy bias for both phylogenetic and ontogenetic fear-relevant stimuli and shock. In the second phase subjects were actually exposed to the random slide/outcome presentation. Only high-fear subjects demonstrated a covariation bias which was specific to phylogenetic fear-relevant slides and shock, indicating all other biases were effectively attenuated.

Analysis of Variance↗

Conditioning with facial expressions of emotion: effects of CS sex and age.

Two experiments examined the effects of facial expressions of emotion as conditioned stimuli (CSs) on human electrodermal conditioning and on a continuous measure of expectancy of the shock unconditioned stimulus. In Experiment 1, the CS+ was a picture of a person displaying an angry face and CS- was a neutral face. For half of the subjects, the expressions were depicted by males, for the other half by females. Male subjects showed larger skin conductance responses to pictures of males than did females. The responding of female subjects was the same regardless of the sex of the person in the picture. In Experiment 2, the CS+ and CS- were pictures of an angry or a happy face. For half of the subjects, the expressions were depicted by adult males, for the other half by preadolescent males. Subjects displayed greater differentiation when an adult male depicting anger was employed as the CS+ than when a preadolescent male depicting anger was the CS+. There were no differences when an adult or a child displayed happiness.

Adolescent↗

Effects of selective drugs for dopaminergic D1 and D2 receptors on conditioned locomotion in rats.

Classically conditioned locomotor activity has been demonstrated by pairing injections of dopamine agonists or antagonists with specific environmental stimuli. The present studies investigated conditioning using drugs with varying selectivity for the dopamine D1 or D2 receptor. Experiment 1 assessed conditioning in groups of rats using the indirect acting agonist (+)-amphetamine (2.0 mg/kg), and the D1 agonist SKF 38393 (10.0 mg/kg), the D2 agonist quinpirole (2.5 mg/kg), the D1 and D2 antagonists, SCH 23390 (0.05 mg/kg) and metoclopramide (25.0 mg/kg), respectively. Paired groups received nine 2-h drug-environment (automated activity monitoring chambers) pairings whereas Unpaired groups received the stimuli explicitly unpaired. Test revealed conditioned hyperactivity with each agonist and metoclopramide whereas conditioned hypoactivity was seen with SCH 23390. Experiment 2 assessed the interaction of these agonists and antagonists on the establishment of conditioned activity. Paired groups received an agonist and antagonist during conditioning sessions. SCH 23390 blocked conditioning based on (+)-amphetamine and SKF 38393 but not quinpirole. Metoclopramide (10.0 mg/kg) blocked conditioning based on quinpirole but not SKF 38393. Metoclopramide (25.0 mg/kg) also did not block (+)-amphetamine-induced conditioning. These studies suggested that drug-induced alterations at either D1 or D2 receptors may be involved in conditioned locomotion.

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

Scopolamine produces environment-specific conditioned activity that is not blocked by pimozide in rats.

A classical conditioning paradigm was employed to determine if the stimulant effects of the anticholinergic scopolamine could show conditioning. In experiment 1 rats had 12 60-min pairings of scopolamine (1.0 or 8.0 mg/kg, IP) with a distinctive environment that monitored horizontal and vertical activity. Experimental (paired) groups received the drug 30 min prior to each session, whereas control (unpaired) groups received saline. Following each session the Paired groups were injected with saline, and the Unpaired groups received the same doses of scopolamine. After every fourth pairing a test session assessed conditioning by comparing activity of paired und unpaired groups in response to saline. Scopolamine enhanced horizontal activity, although conditioning was seen only with 8.0 mg/kg. The low dose increased vertical activity, whereas an initial decrease was observed with 8.0 mg/kg. However, conditioned vertical activity was seen with both doses. Experiment 2 assessed the possible role of dopamine in conditioning with 8.0 mg/kg scopolamine. Rats treated as in experiment 1 were additionally given 0.4 mg/kg pimozide 4 h prior to each pairing session. Pimozide did not block scopolamine's stimulant effect. Conditioned horizontal and vertical activity were also observed, suggesting that this effect may be mediated by direct changes within cholinergic systems.

Animals↗

Stimulant effects of apomorphine and (+)-amphetamine in rats with varied habituation to test environment.

The stimulants (+)-amphetamine and apomorphine are known to increase motility and induce stereotypy in rats. The present study examined the effects of an habituation period immediately prior to injection on these stimulant effects. Male Wistar rats received doses of either drug including 0, 0.01, 0.1, 0.25, 1.0, 2.0 and 4.0 mg/kg in a random order. Activity was assessed in 6 automated chambers where horizontal and vertical activity were tabulated hourly for 4 hours. Initially all rats had equal exposure to the chambers over 5 days. In the subsequent drug phase, habituated rats were placed in the chambers for the 1-hr period prior to each injection whereas non-habituated rats were in their home cages at the corresponding time. (+)-Amphetamine stimulated horizontal activity, although under either condition the effect was not seen until the second hour post-injection, but lasted until the fourth hour. Vertical activity was similarly enhanced, but with habituation there was a significant stimulant effect in the first hour as well. With apomorphine the habituation period resulted in an absence of a significant stimulant effect. Non-habituated rats showed a significant stimulant effect with the highest dose only on vertical activity in the first hour and a stimulant effect with horizontal activity in the second hour. It is suggested that the relative novelty of the environment affected the behavioral response to apomorphine but not to (+)-amphetamine. Furthermore, the activating effects accompanying drug administration should be taken into account as a factor affecting responses to drugs. Such environmental factors may be of particular importance when considering drugs with a short duration of action.

Animals↗

The dopamine D-2 agonist quinpirole produces environment-specific conditioned activity.

The stimulant effects of various dopamine agonists can become conditioned to the particular environment with which they are repeatedly paired. The present study assessed the ability of the selective dopamine D-2 agonist quinpirole (2.5 mg/kg) to similarly show environment-specific conditioning. Rats in Paired and Unpaired groups (both n = 12) received 12 pairings of a unique environment with quinpirole or saline, respectively. Horizontal and vertical activity were automatically measured during the 60-min sessions. Home cage injections were given after each session and involved administration of saline or quinpirole to rats, whichever they did not have during the session. Intermittent tests for conditioned activity were given wherein both groups received saline prior to being placed in the chambers for 60 min. Quinpirole enhanced horizontal activity. Stimulant effects on vertical activity were also observed although they appeared after an initial suppression of the response. Conditioned activity was observed on the saline tests as the Paired group was significantly more active than the Unpaired group on each measure. The present findings suggest that enhanced stimulation of the D-2 receptor can produce environment-specific conditioned activity. Consequently, researchers using quinpirole should take this factor into consideration, particularly if utilizing chronic drug treatment.

Animals↗

Stimulant effects of (+)-amphetamine are influenced by methodological variables.

1. The locomotor effects of (+)-amphetamine were examined in two groups of rats placed in chambers of different sizes. 2. Prior to drug exposure, rats in large chambers were more active, as measured on a rating scale. 3. Under amphetamine, ratings discriminated the 2.5 mg/kg dose from both saline and 0.25 mg/kg without observed differences between the latter two. Scores recorded automatically in the large chambers showed enhanced horizontal activity with both doses, although they did not differ amongst themselves. 4. Methodological variables, including the size of apparatus and recording technique may influence observed effects of amphetamine, and suggest these variables be taken into account when studying drug effects.

Animals↗

Effects of extinction, pimozide, SCH 23390, and metoclopramide on food-rewarded operant responding of rats.

The similarity in the pattern of responding produced by extinction and dopamine (DA) receptor blockers has led to the suggestion that DA neurons may participate in the usual effects of reward on behaviour. The purpose of the present study was to evaluate the effect of receptor-subtype specific DA antagonists on food-rewarded operant responding. Rats were trained to lever press for food on a variable interval 30-s schedule. They then received one of the following treatments prior to testing on the next 5 days: saline, nonreinforcement, the DA receptor blocker pimozide (0.5 or 1.0 mg/kg), the D1 receptor blocker SCH 23390 (0.01, 0.05, 0.1 mg/kg), and the D2 receptor blocker metoclopramide (1.0, 5.0, 10.0 mg/kg). Nonreinforcement resulted in both intra- and intersession declines in responding. The drugs produced dose-dependent decreases in overall responding. Additionally, both doses of pimozide and the higher doses of SCH 23390 and metoclopramide altered intrasession patterns of responding when compared to saline, with their greatest effect being in the latter portion of the session. Intersession declines were seen with the highest doses of SCH 23390 and metoclopramide and control studies showed that these declines could not be attributed to a buildup of the drug with repeated dosing. It was concluded that both D1 and D2 receptors participate in the control of behaviour by reward.

Animals↗

Environment-specific conditioning and sensitization with (+)-amphetamine.

Learning variables have an important role in determining the behavioral effects of some pharmacological treatments. Environmental control of sensitization and conditioning of the stimulant effects of (+)-amphetamine (AMPH) were studied in two experiments. Rats were given 6 1-hr habituation sessions in automated activity chambers conducted every second day. Two days later the 12 rats in the paired group in each study received AMPH (2.0 mg/kg) followed immediately by placement in the chambers for 1 hr whereas rats in the unpaired groups received saline. All rats were injected the following day and left in their home cages afterwards. At this time the paired groups received saline and the unpaired groups received AMPH. Three days later a second pairing and subsequent home cage injection was administered, using the same procedure. Immediately prior to the test session (4 days after the last pairing session) all rats in the sensitization experiment received AMPH and those in the conditioning study received saline. During pairing sessions AMPH treated rats exhibited more vertical activity than controls. On the saline test session in the conditioning study there was still a significant group difference demonstrating environment-specific conditioning. There was no evidence of sensitization on vertical activity; however, a significant difference in horizontal activity was seen on the AMPH test session. Results suggest that these two phenomena can be dissociated behaviorally and may not follow the same time-course.

Amphetamine↗

The effects of (+)-amphetamine and apomorphine on responding for a conditioned reinforcer.

Two psychomotor stimulants, (+)-amphetamine and apomorphine, were examined for effects on associative learning and responding for a conditioned reinforcer. The experimental phases included: preexposure to an operant test chamber with two levers, each of which produced a neutral stimulus when pressed; pairings of one stimulus with food; and a subsequent test of lever pressing for the two stimuli. Groups of food deprived rats (n = 8-12) were given IP injections of one stimulant prior to each pairing or testing session. Given during pairings, (+)-amphetamine produced a dose-related attenuation of responding for the conditioned stimulus in the test; doses of 0.5, 1.0 and 2.0, but not 0.25 or 4.0 mg/kg, given during the test enhanced responding, as did 0.5 mg/kg given in both phases. Apomorphine did not significantly alter responding during testing when administered in either the pairing (0 0.75 mg/kg) or test (0.5 1.0 mg/kg) phase. The results suggest that the modulation of conditioned reinforcement by psychomotor stimulants may occur through a presynaptic influence. Furthermore, the results with (+)-amphetamine suggest that this drug differentially affects the learning of an association between a conditioned and unconditioned stimulus versus the acquisition of responding for that conditioned stimulus.

Animals↗

Receptor subtype-specific dopaminergic agents and conditioned behavior.

Dopaminergic neurotransmission has been implicated in reward-related learning. With the advent of pharmacological agents that are relatively specific for D1 and D2 dopamine receptors, it has become possible to assess the role of these receptor subtypes in this form of learning. Antagonist studies have shown that either D1 or D2 receptor blockers produced extinction-like effects on operant responding for food, water or brain stimulation reward and in drug self-administration paradigms. They also blocked place preference learning based on amphetamine. Agonist studies showed that D2, but not D1 agonists were self-administered, produced place preferences and enhanced responding for conditioned reward. It may be that the dopaminergic signal at the D1 receptor is important for the establishment and maintenance of reward-related learning. From this point of view the effects of D1 antagonists can be understood. D2 antagonists may produce extinction-like effects because they lead to increased dopamine release and, therefore, indirectly mask the dopamine signal at the D1 receptor. D1 agonists may fail to produce reward effects because they, unlike D2 agonists, directly mask the dopaminergic signal at the D1 receptor.

Animals↗

Receptor subtype-specific dopaminergic agents and unconditioned behavior.

When all of the data concerning the role of D1 and D2 receptors in the control of unconditioned behaviors are taken together a fairly consistent picture begins to emerge. Considering first the normosensitive animals, it appears that D1 and D2 receptors are interdependent in their involvement in the control of locomotor activity. Stimulation of either receptor subtype leads to increases in activity although D2 agonists generally have a larger effect on activity than D1 agonists. Subeffective doses of D1 and D2 agonists (or D1 and D2 antagonists) have a synergistic action when co-administered. Injections of antagonists specific for either receptor subtype leads to a decrease in unstimulated locomotor activity or a diminution in the effects of agonists stimulating either receptor subtype. Besides locomotor activity, stimulation of D2 receptors produces yawning but a consistent effect on grooming has not been seen; D2 receptor stimulation also produces stereotyped behaviors. Again, there seems to be an interdependence between the two receptor subtypes; yawning or stereotypy produced by D2 receptor stimulation is blocked by either D2 or D1 antagonists. Stimulation of D1 receptors produces grooming and small perioral movements but not stereotyped behaviors like those typically seen following large doses of D2 agonists or DA agonists not specific a receptor subtype. Unlike D1 receptor-stimulated locomotor activity which is antagonized by D2 receptor blockers, grooming and perioral movements are not (but see Ref. 81). Thus, D1 receptor-mediated grooming and perioral movements seem to be exceptions to the otherwise general finding that co-stimulation of the two receptor subtypes needed for the expression of D1 or D2 agonist effects in normosensitive rats and mice. The apparent need to stimulate both D1 and D2 receptors to produce locomotor and some other unconditioned behaviors in normosensitive animals is lost in chronically denervated animals that are supersensitive to the effects of DA or DA agonists. However, there appear to be important species differences. Generally, in rodents undergoing unilateral or bilateral 6-OHDA-induced destruction of the nigrostriatal DA system, the locomotor effects of D1 agonists are not blocked by D2 antagonists and those of D2 agonists are not blocked by D1 antagonists. Similar results have been reported following chronic treatments with catecholamine depleting drugs. Thus, stimulation of either D1 or D2 receptors alone in DA supersensitive rodents appears to be sufficient to produce locomotor activity. In primates made DA supersensitive either with MPTP or as a result of Parkinson's disease, on the other hand, D2 but not D1 agonists are effective in reversing locomotor deficits.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Automating the measurement of locomotor activity.

General locomotor activity is assessed in many ways ranging from observer ratings to sophisticated computer-assisted electronic monitoring with the aim of determining the unconditioned and conditioned effects of various pharmacological compounds. A system was constructed utilizing 6 independent test chambers each equipped with 14 infrared emitters and detectors arranged in two tiers and controlled by a microcomputer. The effects of the stimulant, d-amphetamine and its antagonism by the tranquilizer, pimozide, on unconditioned and conditioned activity as assessed using this system were found to be almost identical to results obtained using observer rating techniques. Other data showed that activity assessed by the system was subject to habituation and that this learning interacted with the effects of some drugs. Activity as measured by the system showed dose and time effects of various stimulants assessed over a 6 hr test period. Finally, the breakdown of activity into counts on the upper and lower tier of beams resulted in the finding that these two components of behavior were differentially affected by stimulants. These results demonstrate the validity and reliability of automated systems for assessing locomotor activity and show their promise for gaining further insight into the elements of behavior that are affected by various drugs.

Animals↗