Synthesis of potential hydrazinoamine tuberculostatics. XIV. Reactions of 2-aminoethylhydrazine with ketones

The role of brain catecholaminergic mechanisms in habituation of activity was investigated in rat pups treated with 6-hydroxydopamine (6-OHDA). Intracisternal administration of this agent in the neonatal period resulted in a permanent and significant depletion of brain dopamine to 35.5% of controls while brain norepinephrine remained unchanged. Activity levels in normal developing rat pups increased rapidly between 15-22 days, then declined at maturity (26 days), while activity in 6-OHDA treated animals during this peak period of behavioral arousal increased to a significantly greater degree than that of their littermate controls. Habituation of activity, defined as the decrement of spontaneous activity, was calculated by regression over the first 30 min of observation. At both 5 and 8 days of age 6-OHDA and control rat pups exhibited low levels of activity whose decrease with time did not differ significantly and this pattern continued through 12 days of age. However, by 15 days of age activity in control animals declined by 19% each 10 min period compared to only a 10% decline found in 6-OHDA animals. At 19 days normal rat pups declined by 10% compared to a significantly reduced decrement of 3% found in treated animals, but these differences were no longer apparent by 22, 26, or 29 days of age. Our results are consistent with the notion that habituation of activity is a complex phenomenon mediated in part by catecholaminergic systems.     

Feeding, activity, and body temperature following 6-hydroxydopamine lesions in diabetes (db/db) mice.

Reductions in central catecholamines produced by intraventricular injections of 6-hydroxydopamine (6-OHDA) cause weight loss and decreased plasma glucose in diabetes (db/db) mice. The present study examined the effects of this treatment in short-term (64-day) and long-term (120-day) survival groups of female diabetes (C57 BL/KsJ-db/db) and lean mice. Phenotypically heterozygotes (db/m) and homozygotes (m/m) were used as controls. Diabetes Ss treated with 6-OHDA decreased food intake, lost weight, and maintained a lower weight than vehicle-treated controls until vehicle-treated Ss began to enter the terminal stages of the syndrome, indicated by a loss of body weight. Diabetes Ss given 6-OHDA lost weight despite reduced body temperatures and activity levels. Blood glucose levels were always lower in 6-OHDA than in ad lib fed vehicle-treated db/db Ss. The 6-OHDA treatment also improved pancreatic islet granulation. Pair feeding vehicle-treated with 6-OHDA-treated db/db Ss did not halt weight gain in the vehicle-treated group. However, measurement of carcass fat indicated similar losses in db/db-6-OHDA Ss and vehicle-treated Ss when the vehicle group was pair-fed with lean controls. Treatment with 6-OHDA produced long-term improvement in the diabetes syndrome, but the decreased body weight of the 6-OHDA-treated diabetes Ss could not be completely accounted for by changes in food intake or energy expenditure. (43 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cold water stress abolishes hyperactivity produced by cortical suction lesions without altering noradrenergic depletion.

Through the 30-day postoperative period following focal right hemisphere cortical suction lesions, lesioned and sham-operated control male Sprague-Dawley rats were placed in cold water for 5 min either 4 times at weekly intervals, once during the 1st postoperative week, or not at all. Results indicate different effects of the swim on lesioned and control Ss. Stress at weekly intervals produced hyperactivity in controls but weekly stress in lesioned Ss blocked the development of their expected hyperactivity. A single stress experience occurring 1 wk postoperatively was also sufficient to block the development of hyperactivity in lesioned Ss. Stress, although affecting behavior, did not alter the pattern of norepinephrine depletions in lesioned Ss. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of preference for nutritive over nonnutritive suckling in albino rats.

Investigated nutritive vs nonnutritive suckling in 48 10–21 day old Sprague-Dawley rat pups in a spatial discrimination task. Ss preferred nutritive to nonnutritive suckling on their anesthetized mother at l7 and 21 days of age, but no preference was apparent in 10- and 12-day-old Ss. Rearing in isolation from the mother during Days 11–26 did not impair the development of preference for nutritive suckling in 16 17-day-old Ss. Thus, the appetitive component of suckling of infant rats, like the consummatory component, appears to come under the direct control of nutritional factors at the start of the weaning period. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Validation of a classroom observation code for hyperactive children.

Devised a classroom observation code that would identify hyperactive children reliably. A 14-category observation code was used to record the classroom behavior of 60 6–12 yr old children referred to an outpatient clinic for hyperactivity and 60 same-sex normal children. The overall mean phi coefficient for interval agreement was .76, indicating adequate interobserver reliability. Ss referred for hyperactivity had significantly higher scores than comparison Ss on 12 categories. There was greater within-S variability in the hyperactive group. Motor activity for both groups was significantly inversely related to age. The behavior frequencies during initial and later observations were not significantly different, indicating a lack of systematic observer effects on the S's behavior. However, there was overlap between the hyperactive and comparison Ss for all observation categories. Poor discrimination between the groups was therefore obtained with single-category criteria. Two-category criteria, especially the dyad interference and off task, substantially increased the code's discriminability, resulting in relatively few false positive and few false negative classifications. The code is felt to be a reliable and valid instrument for the objective quantification of classroom behavior in hyperactive children. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The dorsal tegmental noradrenergic projection: An analysis of its role in maze learning.

Evaluated the hypothesis that the noradrenergic projection from the locus coeruleus (LC) to the cerebral cortex and hippocampus is an important neural substrate for learning. Four experiments were conducted with 61 male Wistar rats. Maze performance was studied in Ss receiving either electrolytic lesions of LC or 6-hydroxydopamine (6-OHDA) lesions of the dorsal tegmental noradrenergic projection. The LC lesions did not disrupt the acquisition of a running response for food reinforcement in an L-shaped runway, even though hippocampal-cortical norepinephrine (NE) was reduced to 29%. Greater telencephalic NE depletions (to 6% of control levels) produced by 6-OHDA also failed to disrupt the acquisition of this behavior or to impair the acquisition of a food-reinforced position habit in a 'T'-maze. Neither locomotor activity nor habituation to a novel environment was affected by the 6-OHDA lesions. Ss with such lesions were, however, found to be significantly more distractible than were controls during the performance of a previously trained response. The hypothesis that telencephalic NE is of fundamental importance in learning was not supported. The data suggest that this system may participate in attentional mechanisms. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of color stimulation on performance and activity of hyperactive and nonhyperactive children.

Conducted a theoretically based investigation of color stimulation effects on hyperactivity. Moderating variables likely to be important in investigating these effects were identified as the nature of the task (learning and sustained attention), task factors that could provide changes in level of stimulation (task exposure, temporal placement of added stimulation), and child characteristics (sex). 66 hyperactive and 80 normal 1st–6th graders were administered a concept task and a vigilance task under 1 of 3 conditions: no stimulation added, stimulation added early, or stimulation added late. Findings show that stimulation added early or late to a sustained attention task could normalize the performance of hyperactive Ss and reduce their activity. When the task involved acquisition of new information, stimulation added late reduced the activity of the hyperactive Ss. Stimulation effects on concept task performance were, however, less interpretable due to task floor-effects. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cocaine-induced effects on isolation stress in neonatal rats.

The effects of cocaine administration on isolation-induced vocalizations and activity levels in 10-day-old rat pups were examined. Day 10 pups given cocaine (1.25, 2.5, 5, 10, and 20 mg/kg ip) vocalized significantly less than their caffeine- (10 mg/kg) and saline-administered siblings during a 5-min isolation period. Cocaine- and caffeine-administered pups also demonstrated a significant increase in overall activity compared with controls. In addition, ip administration of the dopamine antagonist haloperidol (0.5 and 1.0 mg/kg) before 1.25 and 2.5 mg/kg cocaine produced a significant elevation in vocalizations compared with saline pretreatment, which indicates a blocking of cocaine's effect on calling behavior. These results suggest that the endogenous dopamine system involved with reinforcement and reward may quell the stress of isolation in the infant rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Review of follow-up and follow-back studies of childhood hyperactivity.

The outcome for children diagnosed as hyperactive is viewed as an important perspective in validating the disorder. Accordingly, a review of 17 follow-up and 7 follow-back studies is presented that assesses the available evidence relating to this issue. In follow-back studies, Ss were chosen and assessed on the basis of past information (i.e., a diagnosis of hyperactivity contained in medical records) that they were hyperactive in childhood. Methodological problems are identified and discussed. In particular, it is noted that all of the follow-up studies failed to use psychiatric controls; this makes it difficult to draw conclusions about the diagnostic validity of the concept of hyperactivity. Four of the follow-back studies did use psychiatric controls, but conclusions are limited by the atypical nature of their S groups. It has been demonstrated, however, that hyperactives in late adolescence and early adulthood, as compared with normal controls, experience difficulties in many areas of social functioning and personal well-being. (71 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects on body weight of central 6-hydroxydopamine lesions in obese (ob/ob) and diabetes (db/db) mice.

Obese (ob/ob) and diabetes (db/db) mice are genetic mutants that have been shown to have altered levels of central catecholamines (CAs) as well as syndromes of obesity, hyperphagia, and hyperglycemia. Because the CAs, and particularly norepinephrine (NE), are implicated in the control of feeding, levels of central CAs were experimentally reduced in ob/ob and db/db mice to investigate the role of CAs in these cases of spontaneously occurring obesity. Lesions produced by 6-hydroxydopamine (6-OHDA) were used to produce large depletions of NE and dopamine (DA) in both ob/ob and db/db mice and in lean control Ss of the same background strains. In the db/db but not the ob/ob, central CA depletion was accompanied by a significant and persistent weight loss and by a reduction in plasma glucose levels when compared with vehicle-infused controls. Treatment with the NE uptake blocker desipramine (DI) prior to 6-OHDA infusions attenuated NE but not DA depletion. Diabetes Ss that received DI pretreatment showed a weight loss and decrease in plasma glucose proportional to the amount of NE depletion. Lean Ss that received the 6-OHDA treatments showed only a transient weight loss and no significant change in blood glucose. Abnormalities in central noradrenergic systems may account for part of the obesity syndrome in the diabetes mouse. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behaviorally functional opioid systems in infant rats: II. Evidence for pharmacological, physiological, and psychological mediation of pain and stress.

Two experiments, with 160 10-day-old Sprague-Dawley rat pups, examined the behavioral characteristics of the neonatal opioid system during distressful situations, using a modification of the hot-plate paw-lick test. Ss were analgesic to heat following intraperitoneal morphine (0.5 mg/kg). Subcutaneous naloxone (0.5 mg/kg) prevented the analgesia. Morphine analgesia was significantly greater in Ss group-isolated from the dam. Saline controls group-isolated from the dam exhibited longer latencies than their nest-housed siblings. Individual isolation for 5 min markedly increased paw-withdrawal latency, and this effect was naltrexone reversible. Analgesia was not seen when Ss were tested directly from the nest or when grouped with others for 5 min. It is suggested that the opioid systems for stress and pain are functional in 10-day-old rats and that short-term isolation from the dam is a probable natural stressor modulated by endogenous opioid release. (51 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Suckling behavior and intake control in the developing rat pup.

Studied the behavioral development of suckling and intake control in 2 experiments with Charles River CD strain rat pups. Ss were observed at the initiation, during the course, and at the termination of suckling from their anesthetized mothers. Diet was delivered intraorally through a fine tongue cannula which enabled control of timing and volume. The control of diet intake and the behavior at termination of suckling showed correlated changes from 5 to 20 days of age. When deprived of suckling (and food and water) for 8 hr, 5- and 10-day-old Ss consumed large volumes of diet (10% of body weight or greater) and terminated suckling only in the presence of extreme gastrointestinal filling. These Ss were immediately lethargic and slept after intake termination. Five-day-old Ss persisted in reattaching to the nipple when manually stimulated; 10-day-old Ss eventually refused to reattach. In contrast, 20-day-old Ss consumed more moderate volumes of diet (5% of body weight). These Ss also remained awake for a period after feeding and engaged in the exploratory and grooming activities characteristic of adult rats at the termination of feeding. These observations demonstrate major changes in suckling behavior during development. They suggest that intake control processes shift from indirect to direct and become more effective and specifically food intake related in older pups. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Subcategorizing hyperactivity: The Stony Brook Scale.

Evaluated an assessment procedure based on the conceptual framework of J. Loney et al (see record 1979-23964-001) for documenting and validating independent dimensions of hyperactivity and aggression. Three samples of children were employed: 92 1st and 2nd graders referred for diagnosis of possible hyperactivity, 62 of these Ss who were confirmed to be hyperactive, and a replication sample of 44 equally hyperactive children in kindergarten through 5th grade. The results of factor and correlational analyses indicated that the Stony Brook Scale (SBS) independently assessed hyperactivity and aggression in the highly hyperactive Ss (but not in the heterogeneous sample), that the SBS was superior in this regard to other scales, and that SBS factors correlated meaningfully with 2 other teacher-rating scales: the Behavior Problem Checklist and the Conners Teacher Rating Scale. (13 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of intracisternal 6-hydroxydopamine treatment on acquisition and performance of rats in a double T-maze.

136 male Sprague-Dawley rats in 4 experiments were subjected to various treatments with 6-hydroxydopamine (6-OHDA) to produce decrements in brain catecholamine content either before or after learning to respond in an appetitively motivated double –T maze task. Intracisternal injections of 6-OHDA not only impaired acquisition of the required behavioral response but also decreased performance of Ss which had previously acquired the task. Although reduced food consumption found in 6-OHDA-treated Ss may contribute to the observed deficits in –T maze responding, the behavioral deficit produced by 6-OHDA injection did not seem to be due only to a simple decrease in food intake. The decrements in acquisition and performance were clearly related to amount of central catecholamine depletion produced by 6-OHDA treatment. Further analysis suggested that the behavioral deficits were more related to the reductions in dopamine than they were to the depletion of brain norepinephrine. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social facilitation and inhibition to hunger-induced killing by rats.

Gave 162 male Long-Evans rats different types of experiences to alter their mouse- and rat-pup-killing behavior. First, hungry Ss given considerable experience in mouse killing did kill rat pups, whereas inexperienced Ss were unlikely to kill pups. Second, nonkilling experiences subsequently inhibited hunger-induced mouse killing. Nonkilling experience was given by presenting rat pups and mice to food-satiated Ss and by presenting rat pups to hungry Ss. Inhibition was greater when pups were presented to satiated Ss rather than to hungry, and when pups, rather than mice, were used as inhibitory stimuli. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of early social deprivation on emotionality in rats.

Following parturition, 95 male Holtzman albino rat pups were separated from their mothers and randomly assigned to rearing conditions (a) with mother and peers, (b) with mother without peers, (c) in incubators with peers, or (d) in incubators in isolation. At 65 days of age Ss were tested daily in an open field for 3 min. over 6 consecutive days. At 113 days of age, Ss were restrained and presented a mild auditory stimulus and subsequently a noxious shock stimulus while heart rate recordings were taken. Higher emotionality in maternally-deprived Ss was evidenced in longer emergence latencies, lower ambulatory scores, and higher urination frequencies in the open field. Maternally-deprived Ss also gave larger heart rate responses to auditory and shock stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Biphasic effects of ethanol on open-field activity: Sensitivity and tolerance in C57BL/6N and DBA/2N mice.

Male C57BL/6N (C57) and DBA/2N (DBA) inbred mice were found to differ in open-field behavior after an acute ip injection of ethanol and in the development of tolerance to repeated injections. DBA Ss showed only increased activity for 28 min after ethanol doses up to 2.67 g/kg when compared with saline-injected controls; C57 Ss showed dose-related increases in activity during the first 4 min, followed by dose-related decreases in activity. The effects endured for at least 60 min after injection in both strains. In a 3rd experiment, Ss were injected daily with saline or 2 g/kg ethanol and tested on Days 1, 5, 9, and 13 for open-field activity. On the 17th day, all Ss were tested after an ethanol injection; neither strain showed tolerance to the activity-stimulating effect of ethanol. Some evidence for tolerance to the effect of ethanol to reduce activity in C57's was found. In a 4th experiment, twice-daily injections of ethanol for 10 days produced marked tolerance to the depressant effect of an injection on the 11th day in C57 Ss; no tolerance to the stimulant effect of ethanol was found. DBA Ss injected twice daily for 19 days did not display tolerance when tested on Days 10 or 20, instead showing more marked stimulation of activity after ethanol than mice treated chronically with saline. Implications for the genetic control of responses to ethanol are discussed. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of localized lesions of n. accumbens on morphine- and amphetamine-induced locomotor hyperactivity in the C57BL/6J mouse.

In 2 experiments with 46 C57BL/6J mice, it was found that Ss became hyperactive to increasing doses of morphine sulfate. This response was similar to locomotor hyperactivity induced by amphetamine. Lesions and chemical blockade of posterior nucleus accumbens abolished amphetamine-induced hyperactivity and reduced but did not abolish the morphine response. Results demonstrate that response to the drugs is mediated by overlapping but noncongruent neural systems. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of preadolescent experiential factors on the development of sexual behavior in albino rats.

Weaned 48 male Charles River rat pups at 14 days of age and then maintained them in groups or isolation within either restricted or play-enriched environments. At approximately 120 days of age, Ss were given 4 mating tests, 7 days apart. Isolation resulted in a marked reduction of Ss exhibiting appropriate sexual behavior. Play-enriched environments significantly decreased aberrant sexual behaviors such as climbing but also tended to reduce rather than enhance the level of sexual responding, as had been predicted. It is suggested that social grooming is likely to be a more critical factor than play in the development of normal sexual behavior in rat pups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhanced frustrative nonreward effect following 6-hydroxydopamine lesions of the lateral septum in the rat.

Tested the effect of local injections of 6-hydroxydopamine (6-OHDA [3 μg/1 μl]) into the lateral septum in a paradigm that leads to an energizing behavior, through a possible frustrative effect, induced by partial or total omission of reward in hungry adult male Sprague-Dawley rats. Biochemical assays in the septum showed that 6-OHDA reduced endogenous dopamine and, to a lesser extent, noradrenaline concentrations and left intact noncatecholaminergic neurons such as serotoninergic terminals. In a double straight alley, Ss were exposed to an acquisition phase, a partially reinforced phase, and an extinction phase. Ss with lesions ran faster for food than controls in the partial reinforcement or extinction situation. The 2 groups also behaved similarly after the 1st 6 trials of the extinction phase. When Ss were tested in a leverpress conditioning task, lesioned and control Ss learned this task equally well, both with respect to the number of leverpresses and the time to obtain a fixed number of food pellets. In the 1st 5 min following the omission of reward, the number of leverpresses increased more for the lesioned Ss than for controls, a difference that disappeared in the later stages of the test. Results indicate that the loss of septal dopaminergic innervation produces behavioral effects similar to those obtained after total destruction of the same areas by electrocoagulation. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)