Behavioral effects on the progeny of mice treated with methylmercury.
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Animals↗
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MIF, TRH, and simian social and motor behavior.
MSH-release-inhibiting factor (MIF) and thyrotropin-releasing hormone (TRH) both have been reported to modify mood and activity in man. These two hypothalamic peptides were given intramuscularly across a 1000-fold dose range to 5 juvenile male M. nemestrina monkeys living in a social group. Motor activity was recorded automatically, and an observer counted various social behaviors. MIF increased motor activity for up to 11 hr. It decreased quiet foraging behavior, but did not change behaviors of social interaction. TRH did not stimulate motor behavior; high doses strongly suppressed it and produced apparent somatic distress. TRH increased behaviors of quiet rest and association and decreased environment exploration and low-intensity dominance behaviors. The lowest dose of TRH increased social play. Two monkeys showed repetitive, stereotyped behaviors even in baseline observations, and certain doses of TRH and MIF may have increased the frequency of these behaviors.
Animals↗
Cholecystokinin accelerates the rate of habituation to a novel environment.
Cholecystokinin (CCK8), an octapeptide present in high concentrations in both gut and brain, has been proposed as a putative satiety signal in a variety of species. Exploratory and social behaviors in particular are inhibited by exogenously administered CCK8. One hypothesis for the mechanism by which CCK reduces feeding and exploration is that CCK8 is reducing arousal and attention to environmental stimuli. This possibility was tested by analyzing the rate of habituation to the novelty of objects placed in an unfamiliar arena. A video-tracking computer-assisted animal behavior monitor measured four parameters of exploratory behaviors in rats pretreated with intraperitoneal CCK8. During the first 30 minutes in the novel environment, CCK8-treated animals showed a reduced latency to cessation of exploration as compared to saline controls. In repeated five minute sessions on consecutive days, CCK8 treatment accelerated the decline in exploration over daily sessions. Pentobarbital, a known sedative, induced low levels of exploration throughout the repeated daily sessions. These data suggest that CCK8 is inducing a more rapid rate of habituation to the novelty of environmental stimuli. An accelerated rate of habituation might underlie some of the satiety-related behavioral effects of this peptide.
Animals↗
Endorphinergic modulation of neural reward systems indicated by behavioral changes.
Experiments were performed in rats expecting and/or having received rewards to see if naloxone-antagonizable changes occur in behavior. It was found that rats expecting to receive candy display a naloxone-blockable increase in nociceptive thresholds and a naloxone-sensitive increase in rearing. Similarly, water-deprived rats expecting to receive water show a naloxone-blockable increase in rearing, whereas thirsty animals not expecting water show no changes in nociception or activity. Naloxone was also found to reduce the consumption of a highly palatable food and to diminish the performance of rats trained to wait in one place to receive candy. The latter indicates that the naloxone effect upon goal seeking is not dependent upon a decrease in general activity. Experiments in highly morphine-tolerant rats maintained on relatively constant morphine concentrations showed that these rats drink chocolate milk in the same way as placebo-treated animals. The same rats were found to fail to decrease their intake to the same extent as placebo-controls when water is substituted for the first time for chocolate milk given regularly every day. This points to the possibility that a negative action of endorphins, that is a decrease in release, decreasing consumption, upon a reduction in the palatability of an expected food, might be absent in highly tolerant animals. It is suggested that endogenous opiate(s) regulate mood as defined by the level of goal-seeking behavior, sensitivity to noxious stimuli and general activity.
Analgesics↗
Long-term behavioral changes in rats following organophosphonate exposure.
The organophosphorus compound soman irreversibly inhibits cholinesterase in both the central and peripheral nervous systems. High doses of this compound produce seizures and death in animals. Surviving animals exhibit neural lesions and behavioral abnormalities. The behavioral effects of a single exposure to soman were evaluated in rats injected with 50 micrograms/kg or 85 micrograms/kg soman or with saline. Each rat was tested for either activity in an open field or performance in a 14 choice point multiple T-maze. All rats were then tested for reactivity to tactile stimuli. Some rats exposed to soman showed increased activity in the open field, learning deficits in the Stone maze, and increased reactivity to tactile stimuli, while others showed behavior similar to that of controls. An increase in reactivity was correlated with increased open field activity and with poor performance in the Stone maze. Rats which had received soman and were abnormal in behavioral tests were more likely to have abnormal brain pathology than rats which had received soman and were normal in behavioral tests.
Animals↗
Interactions between 5-hydroxytryptamine (5-HT) and testosterone in the control of sexual and nonsexual behaviour in male and female rats.
Two 5-hydroxytryptamine2 (5-HT2) agents, ritanserin and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) (both at 0.25 mg/kg IP), were administered to castrated males bearing graded testosterone implants (empty, 2.5-, 5-, and 10-mm length) and to normal and neonatally androgenized ovariectomized females bearing 10-mm testosterone implants. The results indicate that testosterone stimulates male sexual behaviour and appears to have a dose-related anxiolytic effect, but no effect on other nonsexual activities. 5-HT and testosterone had opposite effects on male sexual behavior, with ritanserin (5-HT antagonist) enhancing activity in both sexes and DOI (5-HT agonist) inhibiting behaviour in males, the latter being testosterone-dependent. Independent of testosterone, ritanserin reduced locomotion and exploration and increased anxiety in males, while DOI increased locomotion and exploration in both sexes. Ritanserin had a gender-specific effect on anxiety which was independent of testosterone, since in castrated males it was anxiogenic whether they bore testosterone implants or not, while in females it was anxiolytic whether the female were neonatally androgenized (250 micrograms/pup testosterone proprionate [TP] on day 1) or not. These results show that 5-HT and testosterone have opposite effects on male sexual behaviour and these may be interrelated. In adulthood, their effects on nonsexual activities are not inversely related and are independent of each other in contrast to the relationship seen in the neonatal period.
Amphetamines↗
CNQX infused into entorhinal cortex blocks memory expression, and AMPA reverses the effect.
Rats were trained in a step-down inhibitory avoidance task using a 0.8-mA foot shock and tested for retention 26 days later. Three to five days prior to the retention test they were bilaterally implanted with cannulae aimed at the entorhinal cortex. Ten minutes before testing they received an infusion, into the entorhinal cortex, of vehicle, ciano-nitro-quinoxaline-dione (CNQX; 0.5 micrograms), amino-hydroxy-methyl-isoxalone-propionate (AMPA; 1.0 or 2.5 micrograms), or AMPA (1.0 micrograms) plus CNQX (0.5 micrograms). CNQX blocked memory expression; the effect lasted less than 90 min. AMPA had no effect of its own, but at the lower dose level it counteracted the depressant influence of CNQX. It is not likely that the effect of CNQX could have been due to an influence on performance: In separate sets of experiments the bilateral intraentorhinal infusion of CNQX (0.5 micrograms) 10 min before training did not affect either acquisition or retention of the avoidance task or general activity during 3 min of free exploration in the training box. The results indicate that the integrity of AMPA receptors in the entorhinal cortex is necessary for memory expression.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Effect of threonine on the behavioural development of the rat.
Rats received different levels of threonine (Thr), one, 1.7 and four times the normal dietary intake, from conception to adulthood. The mothers were fed the experimental diets before and during pregnancy. Their offspring received a daily oral load of Thr or placebo until weaning. Thereafter, the juveniles were fed the same diet as their mothers. Morphologic development, ingestive behaviour, homing, and locomotion were observed before weaning. Exploration and spontaneous alternation were studied thereafter. Animals exposed during gestation to 1.7 times the normal Thr intake consumed more food during the test of independent ingestion. Grooming showed inconsistent variations between days 12 and 29 in pups fed 1.7 times the normal Thr intake. Rats performed equally well on the other behavioural tasks independently of the dietary treatment. We conclude that Thr intake as much as four times higher than the levels found in normal diets does not impair the behavioural ontogenesis of the rat.
Amino Acids↗
The effects of atrial natriuretic peptide on the open-field activity of rats. The role of neurotransmitters.
In the present study, four doses (50, 100, 200 or 500 ng per animal) of rat atrial natriuretic peptide (rANP1-28) were tested on the open-field activity of rats following i.c.v. application of the peptide. ANP in doses of 200 ng or 500 ng/rat significantly increased the ambulation activity 15 min after the treatment. However, the effect was transitory; 30 min after application it was no longer observed. When the experimental animals were pretreated with different receptor blockers in doses which per se could not affect the behavioral paradigm, the effect of ANP was completely blocked by haloperidol (a dopaminergic blocking agent), phenoxybenzamine (an alpha-adrenergic blocker) and propranolol (a beta-adrenergic blocker). Atropine, naloxone, bicuculline and methysergide were ineffective. These results suggest that dopaminergic and adrenergic transmitter systems are involved in the ANP-induced locomotor activity of rats.
Animals↗
Neurotransmitter receptors involved in post-training memory processing by the amygdala, medial septum, and hippocampus of the rat.
Rats were trained and tested in habituation to a novel environment and step-down inhibitory avoidance. Immediately after training in each task the animals received intra-amygdala, intraseptal, or intrahippocampal micro-injections of agonists and antagonists of various neurotransmitter receptors. In the habitation task, intrahippocampal, but not intra-amygdala or intraseptal administration of the NMDA receptor antagonist aminophosphornopentanoic acid (AP5, 5.0 micrograms) or of the muscarinic receptor antagonist, scopolamine (2.0 micrograms) caused amnesia and the indirect antagonist of GABA-A receptors, picrotoxin (0.08 microgram), caused retrograde facilitation. Intrahippocampal administration of the respective agonists, glutamate, oxotremorine, and muscimol, had effects of their own opposite to those of the blockers, and norepinephrine (0.3 microgram) caused memory facilitation. In the avoidance task, results obtained with drug infusions given into the three structures were very similar: in all cases, AP5, scopolamine, and muscimol were amnestic, and glutamate, oxotremorine, norepinephrine, and picrotoxin caused memory facilitation. In addition, also in the three structures, picrotoxin counteracted the amnestic effect of AP5 and/or scopolamine and the beta-adrenoceptor blocker, timolol (0.3 microgram), while ineffective on its own, attenuated all the effects of picrotoxin. The results suggest that similar synaptic mechanisms in the amygdala, medial septum, and hippocampus are involved in memory consolidation: NMDA, muscarinic, and beta-noradrenergic receptors stimulate and GABA-A receptors inhibit this process, and beta-noradrenergic receptors modulate the GABAergic synapses. In the avoidance task these mechanisms operate in the three structures: in habituation only those in the hippocampus are operative. Possibly in each structure these mechanisms regulate, if not actually consolidate, a different aspect, component, or form of memory.
Amygdala↗
Effect of forebrain commissurotomy on recovery from unilateral 6-OHDA lesions of the substantia nigra and circling induced by apomorphine.
We studied the influence of transection of the interhemispheric fiber systems between the anterior and posterior commissures on recovery from turning behavior induced by a unilateral substantia nigra lesion in rats. It has been argued that the crossed nigrostriatal projection is involved in this recovery, and its site of crossing has been suggested to lie within the region split. Animals which received this transection did not differ from controls with respect to time-course and extent of recovery from lesion-induced asymmetries within the 7 postlesion days examined. Additionally, the commissurotomy did not prevent apomorphine-induced contraversive circling.
Animals↗
Perinatal alterations of thyroid hormones and behaviour in adult rats.
Several studies have shown the relevance of the neuroendocrinological system in the development and function of the nervous system. In order to observe the influence of thyroid hormones during development on the behaviour of adult rats we induced dysthyroid states during the perinatal period. Results indicate that some behaviours are more susceptible to the action of thyroid hormones than others. We observed that the thyroid hormone deficiency causes an increase of activity in animals in spite of a large period of rehabilitation. Thyroxine-treated rats showed an anxiogenic behavioural pattern in the elevated plus-maze, while animals rehabilitated from perinatal deficit of thyroid hormones showed an anxiolitic pattern. These findings suggest that an excess of thyroid hormones has less effect on behaviour than a deficiency of these hormones.
Aging↗
Effects of the subacute administration of nefiracetam on abnormal behavior in aged rats.
We investigated the effects of nefiracetam on learning and memory by the Morris water maze task and water-finding test, and on emotional behavior by forced swimming, hole-board and open-field tests in old male Kbl Wistar rats aged 90 and 108 weeks. In the water maze task, the acquisition of the task in aged rats was slower than that in young rats. Subacute administration of nefiracetam (1 and 3 mg/kg daily) for 24 days tended to shorten the goal latency to escape onto the platform in a dose-dependent manner in the retention test, conducted 24 days after acquisition training. Nefiracetam (1 mg/kg) administration for 49 days decreased the duration of immobility in aged rats in the forced swimming test. Locomotor activity in young rats during the dark period was significantly higher than that during the light period, while there was no difference in locomotor activity between the light and dark periods in aged rats, suggesting that locomotor activity during the dark period and nocturnal habits may be impaired in aged rats. Subacute administration of nefiracetam for 14 days significantly increased the locomotor activity during the dark, but not light, period in a dose-dependent manner. In addition, nefiracetam given for 38 days, significantly shortened the increased time elapsed before animals started exploring the environment in aged rats compared with young rats in the water-finding tests. These findings suggest that nefiracetam may improve the impaired nocturnal habits and some of emotional behavior in aged rats.
Aging↗
Behavioral effects of exposure to nuclear magnetic resonance imaging: I. Open-field behavior and passive avoidance learning in rats.
The effect of exposure to the magnetic and radio-frequency fields associated with Nuclear Magnetic Resonance Imaging (MRI) on two standard animal behavior tests, was examined in rats. In the first experiment male rats were given a baseline open-field test and 48 hrs later exposed for 22.5 min to a MRI procedure, a sham imaging procedure, or a control condition. Immediately after this exposure period a second open-field test was administered. All animals were given 4 more daily exposures to their respective treatment conditions and after the last exposure period a third open-field test was given. Analysis of open-field ambulation, rearing, and defecation responses indicated no significant effect of exposure to MRI on these behaviours. In a second experiment rats were conditioned in a step-down passive avoidance task and then exposed for 23.2 min (48 hrs later) to MRI, sham imaging, or control conditions. Retention tests for the passive avoidance response were administered after the first and fifth daily exposure to the experimental treatment conditions. No significant effects of the treatment conditions on retention of the avoidance response were obtained and a third retention test 3 months after the second test, also failed to provide any evidence for treatment effects. These results fail to provide any evidence for short or long term behavioral changes in animals exposed to MRI.
Animals↗
Explorative and drinking behavior after prolonged access to alcohol and following chronic piracetam administration in mice.
Male mice with free access to food, water, and alcohol for 44 weeks were deprived of alcohol for 3 days and then segregated into two groups having (HD) and lacking (LD) the alcohol deprivation-induced elevation in intake. On week 47, the HD and LD groups (divided into subgroups matched for drinking) received either vehicle or piracetam (400 mg/kg) for 10 days. On the last treatment day, alcohol was again withheld. Cross-maze exploration and drinking pattern were evaluated on the first and third postinjection days. Control mice, having had no previous access to alcohol, were subjected to the same treatment and tests. There were a greater number of vehicle-treated HDs displaying arm reentries than LDs or alcohol-naive control mice. Further, the control mice drank less alcohol than HDs during the first 1.5 h of renewal access, and more water than the HD or LD group during the remaining 22.5 h. Piracetam improved maze patrolling and arm reentries in alcohol-naive mice, but did not change these measures in HDs and LDs. No effect of piracetam on drinking parameters was revealed.
Alcohol Drinking↗
Genetic control of alcohol deprivation effect in congenic mice.
Male mice of A(4R) and AKM congenic resistant strains, differing in E alpha and D loci of H-2 major histocompatibility complex (MHC) only, were tested for cross-maze exploration and for behavior in unavoidable slip funnel situation. On the following 15 weeks the mice had free access to food, water, and 30% alcohol. On weeks 16-17 the individual alcohol and water intakes were measured before and after 3 days of alcohol deprivation to evaluate the alcohol deprivation effect (ADE), which is known to depend upon both genetic and environmental factors. Unlike AKMs, the A(4R)s displayed shorter latency to start cross-maze exploration, greater time of immobility, less time in avoidance attempts in the slip funnel, and demonstrated negative ADE: the short-term, postdeprivation decrease in alcohol intake. It is concluded that the ADE and some of its predictors depend upon E alpha, and/or D loci of the MHC. In the A(4R) strain, the individual correlation between the ADE and the number of immediate reentries, right, and left turns, differed significantly from zero and from the corresponding values in the AKM strain, suggesting a gene-environment interaction.
Alcohol Drinking↗
A behavioral profile of autoimmune lupus-prone MRL mice.
Manifestations of the human autoimmune disease systemic lupus erythematosus (SLE) include a number of behavioral and cognitive deficits. The present study asks whether neurobehavioral dysfunction is present also in MRL mice that spontaneously develop most of the fundamental immunological aberrations of SLE. There are two congenic substrains of MRL mice that differ in the time of disease onset: MRL-lpr mice develop lupus early and MRL(-)+/+ develop the typical signs of disease relatively late in life. The behavior of these substrains was assessed at 7 to 11 weeks of age, a time that coincides with the onset of disease in MRL-lpr mice and the absence of known lupus symptoms in the MRL(-)+/+ group. When compared to the congenic MRL(-)+/+ control substrain, MRL-lpr mice were spontaneously less active, traversed a crossbeam slower, and ceased responding to the novelty of a new environment sooner. They were also more reluctant to leave their home base or travel far away from it and perseverated in their response bias during extinction and reversal learning. Immunological status was characterized by moderate proteinuria in both substrains and high titers of antinuclear antibodies in MRL-lpr but not MRL(-)+/+ mice. Histological analysis revealed minimal or no signs of joint pathology in MRL-lpr mice. Thus, this study shows the presence of behavioral dysfunction in mice with early stages of autoimmune disease and gives support for the idea that MRL mice may provide a useful model of neurobehavioral dysfunction in SLE. It is suggested that the behavioral profile of MRL-lpr mice may indicate increased "timidity," related to genetics, autoimmunity, or both.
Animals↗
Behavioral effects of subchronic intoxication with parathion-methyl in male Wistar rats.
The behavioral effects of subchronic exposure of male Wistar rats to the organophosphorus compound parathion-methyl (for 6 weeks 1/50 or 1/100 of LD50, PO) were studied. Open-field (OF) and elevated plus-maze (EPM) tasks were used to decide whether or not the compound can affect behavior. Significant effects were measured in the OF activity during the first minute, on the activity of crossing outer squares, increasing latencies to leave center, start of rearing, grooming, and defecation. EPM parameters showed an increased amount of time spent in the open arms and a clear tendency to enter more frequently open arms. The defecation rate in the EPM was significantly decreased. Results are discussed in terms of effects on emotional behavioral components (arousal) and on physiological functioning of the peripheral nervous system (lengthening of latencies).
Animals↗