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Lateral hypothalamic feeding mechanisms: iontophoretic effects of kainic acid, ibotenic acid and 6-hydroxydopamine.

In order to study hunger motivated behavior kainic acid (KA), ibotenic acid (IB) and 6-hydroxydopamine (6-OHDA) were iontophoretically applied to the lateral hypothalamus of rats. Neurotoxins at concentrations between 20-120 mMol were applied with 5-20 microA current for 5-10 min. Tip diameter of glass micropipettes varied between 10-50 micron. Application of KA, IB and 6-OHDA caused temporary body weight loss, hypophagia and hypodipsia. Effects were dose dependent: correlation was found between current strength, tip diameter of pipettes, concentrations of neurotoxins and the extent of cellular damage. Aphagic and adipsic symptoms and the death of animals were only observed after extensive LH lesions. There was no significant difference in food consumption after 24 hr deprivation among groups. Water deprivation and extracellular or intracellular dehydration resulted in a considerable increase in water intake in all animals, however, consumption in lesioned rats was lower than that of controls. These water regulatory disturbances in 6-OHDA treated animals were somewhat less severe. Results show that the bilateral cellular microlesions of the LH and damage of dopaminergic (DA) elements with 6-OHDA both cause disturbances of feeding behavior. Although the severity of symptoms in some respects depends upon the nature of neurotoxic treatment, the basic consequences are essentially similar. It is suggested that the LH "feeding center" and the ascending DA pathways represent a single system involved in the organization of hunger motivated behavior.

Animals↗

Low level lead exposure during lactation increases rough and tumble play fighting of juvenile rats.

Lactating rats were given distilled water or distilled water containing 0.067% lead chloride (500 ppm lead) as their sole source of drinking fluid from Days 1-21 of lactation. Activity, social investigation and rough and tumble play fighting behaviors of the offspring were observed on Day 26 and activity and play solicitation behaviors on Day 36. Although lead treatment reduced the mothers' fluid intake, there were no effects on pup growth and activity or on maternal behaviors. When paired with a group-housed stimulus animal on Day 26, lead-treated subjects had increases in the two measures of play fighting (crossover and pinning), and in social investigation, relative to controls. When tested with a scopolamine-treated, non-playful stimulus on Day 36, increased crossover frequencies were observed in lead-treated subjects when compared with controls. Two-min activity levels on Days 26 and 35 were unaffected by lead exposure. These results indicate that social interactive behaviors of juvenile rats are effective tools in the assessment of exposure to toxic substances early in development.

Aggression↗

An analysis of various environmental and specific sensory stimuli on the seizure activity of the Mongolian gerbil.

Mongolian gerbils were subjected to different environmental and specific sensory stimuli to determine the ability of these stimuli to provoke seizures. None of the specific sensory stimuli, somatosensory, olfactory, auditory or visual, were effective in inducing convulsions. This finding does not implicate dysfunctions of the specific sensory pathways in seizure genesis in gerbils. In contrast, several novel environmental stimuli that exposed the animals to a difficult exploratory task (i.e., Y-maze, disk rack, etc.) could trigger seizures, and this suggests that the pathophysiology of epileptiform events in gerbils may have a unique association with exploratory behavior. However, the frequency, latency and severity of the seizures showed no correlation with each other, indicating that these parameters are probably determined by independent factors. Taken together with previous studies on the electrophysiology of the dentate gyrus during exposure to novel experiences, and the anatomical abnormalities found in the hippocampus of the seizure-sensitive gerbil, these behavioral data provide further support for a significant role of the hippocampus in the pathophysiology of seizures in this model of genetic epilepsy.

Animals↗

Dissociation of core and shell single-unit activity in the nucleus accumbens in free-choice novelty.

Core and shell regions of the nucleus accumbens (NAcc) have been implicated in different aspects of goal-directed behavior. To assess these differences at the neuronal level, we evaluated core and shell single-unit activity in eight rats during one-trial, free-choice entry into a novel compartment. Changes in firing rate during approach of (orientation toward) and entry into (nose cross) novelty were assessed relative to a pre-novelty baseline when the animals were behaviorally active. Increases and decreases in neuronal activity were recorded in both regions during both phases of the novelty response. The regional distribution of these responses, however, was significantly different during the approach phase with roughly equal proportions of neuronal excitations (8/29) and inhibitions (6/29) in core but a shift away from excitation (2/40) toward inhibition (12/40) in shell. No regional differences emerged during subsequent approach of the familiar compartment from the novel chamber or during entry to either the novel or familiar compartment. Taken together, our results during approach to free-choice novelty indicate a regional dissociation in NAcc firing rate may play a role in appetitive behavior.

Action Potentials↗

Strain differences in sucrose preference and in the consequences of unpredictable chronic mild stress.

Effects of unpredictable chronic mild stress (UCMS) on anhedonic-like behaviour, physical state, body weight, learning and memory were investigated in three strains of mice. These strains were chosen among 11 strains that were tested in a first experiment for their sucrose consumption and preference for sucrose solutions of different concentrations. In the second experiment, groups of mice of the CBA/H, C57BL/6 and DBA/2 strains were submitted to 7 weeks of UCMS. Measures of the sucrose consumption, the evaluation of the physical state and the measurement of body weight were weekly assessed. Following 4-week period of UCMS, sub-groups of stressed and non-stressed mice were submitted to the spontaneous alternation test in the Y-maze, and then to the water-maze test for spatial learning and memory. UCMS induced a significant decrease of the sucrose consumption in CBA/H and in C57BL/6 but not in DBA/2 mice. The UCMS effect on sucrose intake in CBA/H mice was associated with a body weight loss and a physical state degradation. Spatial learning in a water maze was not disturbed by UCMS, however, a long-term memory impairment was observed in CBA/H stressed mice during a probe test. In the Y-maze, UCMS did not modify spontaneous alternation. These results show both an anhedonic-like and an amnesic effect of UCMS in CBA/H mice. They also reveal a difference of sensitivity to UCMS according to the strain of mice.

Analysis of Variance↗

Regular voluntary exercise reduces anxiety-related behaviour and impulsiveness in mice.

We embarked on a study to delineate the behavioural changes in mice after 4 weeks of voluntary exercise. As an initial behavioural characterization, we exposed the control and exercising mice to a modified hole board and an open field test. As compared to control mice, exercising animals showed clear signs of increased behavioural inhibition (e.g. a longer latency to enter unprotected areas), suggesting increased anxiety in these animals. In addition, the exercising mice were reluctant to spend time in the open field's centre during the beginning of the 30-min open field test, but compensated for this at later times. Paradoxically, the exercising animals showed more rearings on the board of the modified hole board, indicating decreased anxiety. Thus, the behavioural inhibition seen in exercising mice is likely to represent decreased stress responsiveness at the behavioural level which can also be interpreted as reduced impulsiveness. To clarify whether voluntary exercise evolves in more or less anxiety-related behaviour, we exposed animals to the elevated plus-maze and the dark-light box, two selective tests for unconditioned anxiety. Clearly, compared to the control animals, exercising mice spent significantly more time on the open arm of the plus-maze and spent double the amount of time in the light compartment of the dark-light box. Taken together, we conclude that long-term voluntary exercise appears to result in decreased anxiety-related behaviour and impulsiveness. Thus, our observations fit into the concept that regular exercise strengthens endogenous stress coping mechanisms, thereby protecting the organism against the deleterious effects of stress.

Adaptation, Psychological↗

The role of the hippocampus in object recognition in rats: examination of the influence of task parameters and lesion size.

Studies examining the effects of hippocampal lesions on object recognition memory in rats have produced conflicting results. The present study investigated how methodological differences and lesion size may have contributed to these discrepancies. In Experiment 1 we compared rats with complete, partial (septal) and sham hippocampal lesions on a spontaneous object recognition task, using a protocol previously reported to result in deficits following large hippocampal lesions . Rats with complete and partial hippocampal lesions were unimpaired, suggesting the hippocampus is not required for object recognition memory. However, rats with partial lesions showed relatively poor performance raising the possibility that floor effects masked a deficit on this group. In Experiment 2, we used a second spontaneous object recognition protocol similar to that used by the two other studies that have reported deficits following hippocampal lesions . Rats with complete hippocampal lesions were significantly impaired, whereas rats with partial lesions were unimpaired. However, the complete lesion group showed less object exploration during the sample phase. Thus, the apparent recognition memory deficit in Experiment 2 may be attributable to differential encoding. Together, these findings suggest that the hippocampus is not required for intact spontaneous object recognition memory. These findings suggest that levels of object exploration during the sample phase may be a critical issue, and raise the possibility that previous reports of object recognition deficits may be due to differences in object exploration rather than deficits in object recognition per se.

Analysis of Variance↗

Octopus arm choice is strongly influenced by eye use.

This study aims to investigate the octopus' eye and arm coordination and raises the question if visual guidance determines choice of arm use. Octopuses possess eight seemingly identical arms but have recently been reported to show a preference as to which arm they use to initiate contact with objects. These animals also exhibit lateralized eye use, therefore, a connection between eye and arm preference seems possible. Seven Octopus vulgaris were observed during approach, contact initiation and exploration of plastic objects that were positioned on three different levels in the water column. The subjects most commonly used an arm to initiate contact with an object that was in a direct line between the eye used to look at the object, and the object itself. This indicates that choice of arm use is spatially rather opportunistic when depending on visual guidance. Additionally, first contact with an object was usually established by the central third of the arm and in arm contact sequences neighboring arms were the most likely to follow an arm already touching the object. Although results point towards strong eye/arm coordination, we did not find lateralized behavior in this experiment. Results are discussed from a neuro-anatomical, behavioral and ecological perspective.

Animals↗

Physical activity and restlessness correlate with leptin levels in patients with adolescent anorexia nervosa.

BACKGROUND: In food-restricted rats, leptin suppresses semistarvation-induced hyperactivity (SIH) and decreases exploratory behavior. Leptin ameliorates anxiety-related movement in ob/ob mice. In this study, we assessed the relationship between leptin and qualities of physical activity and restlessness in acute anorexia nervosa (AN). METHODS: Serum leptin, body mass index (BMI), % body fat, and self- and expert-ratings of qualities of physical activity and restlessness were assessed in 26 inpatients with acute AN. Accelerometry was also performed. Regression analyses were used to predict activity and restlessness using BMI, % body fat, and leptin levels as predictor variables. RESULTS: Leptin levels significantly contributed to the prediction of all measures of activity and restlessness. CONCLUSIONS: This is the first study linking hypoleptinemia in AN patients to subjective and objective measures of higher physical activity and motor and inner restlessness. Leptin may directly or indirectly (or both) influence behaviors and cognitions contributing to hyperactivity and motor restlessness.

Adolescent↗

Postsynaptic dopamine (D(2))-mediated behavioural effects of high acute doses of artemisinin in rodents.

Artemisinin or qinghaosu is the active principle of quinghao (Artemisia annua L.) developed from Chinese traditional medicine, which is now widely used around the world against falciparum malaria. Behavioural effects of high acute doses of artemisinin were studied on spontaneous motor activity (SMA), exploratory behavior, apomorphine-induced stereotype behavior and pentobarbital sleeping time in mice and rats in order to provide additional evidence on its safety profile on the central nervous system (CNS). Effects of the drug on bromocriptine-induced hyperactivity in short term reserpinised mice were also evaluated. Intraperitoneal (i.p.) injection of artemisinin at doses of 50 and 100mg/kg, significantly (P<0.05) reduced the SMA in mice, prolonged the pentobarbital sleeping time in rats, and attenuated the apomorphine-induced stereotypy in mice. Mice pretreated with reserpine, showed a significant decrease in locomotor activity compared to the saline-treated group. Bromocriptine, a D(2) receptor agonist, induced locomotor activity in mice pretreated with reserpine which was attenuated by artemisinin. The results suggest that artemisinin possesses sedative property, which may be mediated via postsynaptic dopamine (D(2)) receptor in the CNS.

Animals↗

The predatory behaviour of a tramp ant species in its native range.

Workers of the pest ant Paratrechina longicornis participate in a type of group hunting. Each individual forages with its long antennae wide open and moves quickly (6.3 cm/s) along an erratic path surrounded by nestmates behaving in the same way and within range of a recruiting pheromone. They detect prey by contact with successful workers singly capturing and retrieving small prey and seizing larger ones by an appendage. Then they recruit nestmates at short-range; all together they spread-eagle the prey and retrieve them whole.

Animals↗

CNS depressant activity of Lecaniodiscus cupanioides.

The aqueous root extract of Lecaniodiscus cupanioides was used to study the central nervous system depressant activity pattern of the plant. The extract protected mice from strychnine-induced convulsion at 400 mg/kg p.o. and 100 mg/kg i.p. A dose-dependent prolongation of seizure latency was produced at 400 mg/kg, p.o. and 100 mg/kg i.p. for strychnine-induced seizure; and at 400 mg/kg p.o. and 100 mg/kg i.p. for picrotoxin-induced seizure. Moreover, the CNS depressant activity of the extract (200 mg/kg p.o. and 50 mg/kg i.p.) was demonstrated by a significant prolongation of 40 mg/kg, pentobarbitone sleeping time, and significant reduction in exploratory behavior of mice at a dose of 400 mg/kg p.o., with both effects comparable to effects produced by 4 mg/kg chlorpromazine. Acute oral toxicity test, up to 14 days, did not produce any visible signs of toxicity; however, acute (24 h) i.p toxicity test produced a dose-dependent mortality with LD50 of 455.2 mg/kg.

Administration, Oral↗

Cardiotonic and sedative effects of Cecropia pachystachya Mart. (ambay) on isolated rat hearts and conscious mice.

Cecropia pachystachya Mart. is popularly called "ambay" and extensively used in herbal medicine of South America for cough and asthma. In Argentina it grows in neotropical rainforest (Ntr C.p.) and in a temperate region (Tp C.p.). In a previous work we showed their hypotensive properties with different potency and toxicity, and now we studied the Tp C.p. effects in isolated heart from rats and central effects of both plants on the open-field test for mice. Tp C.p. produced a positive inotropic effect on isolated rat hearts, which was not affected by 1 microM propranolol, suggesting that it is not due to a beta-adrenergic effect. In contrast, it was prevented by pretreatment with high [K](o) media, which stimulates the Na,K-ATPase pump, suggesting an inhibition of the pump by "ambay", as digital do. In the open-field test, both Ntr C.p. and Tp C.p. similarly decreased the spontaneous locomotion and exploratory behavior of mice at doses between 180 and 600 mg/kg. Ntr C.p. potentiated the effect of 3 mg/kg diazepam to one similar to 10 mg/kg diazepam, but was not antagonized by 0.5 mg/kg flumazenil. Amphetamine at 5 mg/kg prevented the sedative effect of Ntr C.p. Chromatographic analysis showed that both plants have a qualitatively similar fingerprint but quantitatively differed in at least three components. Although the purpose was not to identify them, both plants have at least 10 compounds. Two of them were in higher amount in Tp C.p. than in Ntr C.p., and then, they could be responsible for the cardiovascular toxicity of Tp C.p. In conclusion, the results suggest that ambay has cardiotonic and sedative properties. The sedative effect could be useful in cough treatment. The extract resulted additive to benzodiazepines but it did not bind to the same site on GABA-A receptor, and it was interfered by the dopamine release produced with amphetamine.

Amphetamine↗

Striatal cell signaling in chronically food-restricted rats under basal conditions and in response to brief handling.

Chronic food restriction increases exploratory behavior, cognitive function, and the rewarding effects of abused drugs. Recently, striatal neuroadaptations that may be involved in these effects were observed. Specifically, D-1 dopamine (DA) receptor agonist challenge produced stronger activation of extracellular signal-regulated kinase (ERK), calcium-calmodulin-dependent kinase II (CaMKII), and the nuclear transcription factor cAMP response element binding protein (CREB) in nucleus accumbens (NAc) of food-restricted (FR) relative to ad libitum fed (AL) rats. Further, when FR rats were injected intracerebroventricularly (i.c.v.) with vehicle (saline) they displayed stronger activation of c-Jun N-terminal protein kinase (JNK), ERK and CaMKII than did AL rats. It is not known to what extent the latter effects represent the basal state of FR rats or an amplified response to the brief handling involved in the i.c.v. injection procedure. Using Western blotting it was found that basal phospho-JNK is higher in caudate-putamen (CPu) and NAc of FR relative to AL rats. Interestingly, brief handling decreased phospho-JNK levels in FR subjects. Basal phospho-ERK1/2 also tended to be elevated in CPu and NAc of FR rats but the elevation was not significant. However, phospho-MEK--the activated kinase upstream of ERK1/2--was significantly elevated in NAc of FR rats. Neither ERK1/2 nor MEK were activated by brief handling. CaMKII was selectively activated by handling in NAc of FR rats, suggesting a state-dependent response to a salient event. Given the established involvement of mitogen-activated protein kinase (MAPK) and CaMKII in synaptic plasticity, learning and memory, the increase in basal phospho-MEK and hyperresponsiveness of CaMKII in NAc may represent adaptive cellular responses to persistent negative energy balance that facilitate associative learning in connection with food-seeking.

Animals↗

Modulation of synaptic zinc in barrel cortex by whisker stimulation.

The cortical representation of the body surface is not fixed, but rather, is continuously modified by ongoing changes in sensory experience. Although the cellular and molecular mechanisms that subserve these changes are uncertain, increasing evidence suggests that synaptically-released zinc may play a role. Zinc is released from a subset of glutamatergic neurons and can modulate postsynaptic excitability by regulating the activation of glutamate and GABA receptor-gated ion channels. Previously, we have shown that whisker plucking, a manipulation commonly used to induce cortical map plasticity, results in a rapid and robust increase in staining levels for synaptic zinc in deprived regions of the barrel cortex. In the present study, we examined the effect of increased whisker activity, analogous to what may happen during tactile learning or exploratory behavior in a natural setting, on synaptic zinc levels in the adult barrel cortex. Our results indicate that stimulation of whiskers caused a selective decrease in zinc levels within layer 4 of the barrel hollow corresponding to the stimulated whisker. Quantitatively, levels of staining were significantly reduced at 3 h, and showed even greater reductions following 12 and 24 h of stimulation. However, these changes were not long-lasting, as levels of staining in the stimulated barrel returned to control values within 24 h after stimulation had ceased. These data indicate that zincergic circuits are highly sensitive to ongoing changes in sensory experience and may participate in moment-to-moment changes in the functional connectivity of the cerebral cortex.

Animals↗

The sectored foraging field: a novel design to quantify spatial strategies, learning, memory, and emotion.

Although Norway rats are naturally gregarious, males typically live alone at some point during adulthood. Different social ecologies often require different learning strategies and also modulate response to stressors and gonadal development. To measure effects of the social environment on the interaction between cognition and emotion during aging, we focused on a natural learning context and devised the sectored foraging field, a progressively difficult spatial navigation task. Here, we describe how this apparatus and protocol permits multiple learning strategies in a minimally stressful environment, enabling finely graded analyses of cognition and emotionality. Male Sprague-Dawley rats living alone throughout adulthood adopted a sex-typic discernible spatial strategy. In contrast, males housed in group contexts utilized an algorithmic kinesthetic strategy, repeating the same motor action until they found food. Removal of food and distal, but not local cues, elicited anxious alertness, particularly in group-housed males. Cognitive performance of group-housed rats subsequent to food and cue removal was significantly impaired, yet enhanced in isolates.

Animals↗

Integrated memory for objects, places, and temporal order: evidence for episodic-like memory in mice.

Human episodic memory refers to the recollection of an unique past experience in terms of what happened, and where and when it happened. Factoring out the issue of conscious recollection, episodic memory, even at the behavioral level, has been difficult to demonstrate in non-human mammals. Although, it was previously shown that rodents can associate what and when or what and where information given on unique trials, it proved to be difficult to demonstrate memory for what, where, and when simultaneously in mammals, without using extensive training procedures, which might induce semantic rather than episodic memory recall. Towards the goal of an animal model of human episodic memory we designed an three-trial object exploration task in which different versions of the novelty-preference paradigm were combined to subsume (a) object recognition memory, (b) the memory for locations in which objects were explored, and (c) the temporal order memory for object presented at distinct time points. We found that mice spent more time exploring two "old familiar" objects relative to two "recent familiar" objects, reflecting memory for what and when and concomitantly directed more exploration at a spatially displaced "old familiar" object relative to a stationary "old familiar" object, reflecting memory for what and where. These results suggest that during a single test trial the mice were able to (a) recognize previously explored objects, (b) remember the location in which particular objects were previously encountered, and (c) to discriminate the relative recency in which different objects were presented. According to the currently discussed behavioral criteria for episodic-like memory in animals, our results suggest that mice are capable to form such higher order memories.

Analysis of Variance↗

Histamine enhances inhibitory avoidance memory consolidation through a H2 receptor-dependent mechanism.

Several evidences suggest that brain histamine is involved in memory consolidation but the actual contribution of the hippocampal histaminergic system to this process remains controversial. Here, we show that when infused into the CA1 region of the dorsal hippocampus immediately after training in an inhibitory avoidance task, but not later, histamine induced a dose-dependent promnesic effect without altering locomotor activity, exploratory behavior, anxiety state or retrieval of the avoidance response. The facilitatory effect of intra-CA1 histamine was mimicked by the histamine N-methyltransferase inhibitor SKF-91844 as well as by the H2 receptor agonist dimaprit and it was blocked completely by the H2 receptor antagonist ranitidine. Conversely, the promnesic action of histamine was unaffected by the H1 receptor antagonist pyrilamine, the H3 receptor antagonist, thioperamide, and the NMDAr polyamine-binding site antagonist ifenprodil. By themselves, ranitidine, pyrilamine, thioperamide, and ifenprodil did not affect IA memory consolidation. Our data indicate that, when given into CA1, histamine enhances memory consolidation through a mechanism that involves activation of H2 receptors; however, endogenous CA1 histamine does not seem to participate in the consolidation of IA memory at least at the post-training times analyzed.

Animals↗