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PubMed1985

Some behavioral factors related to the effects of cold-restraint stress in rats: a factor analytic-multiple regression approach.

Recently, some individual differences in rats have been shown to be related to stress-induced physiological responses. As yet there has been no attempt to incorporate measurement techniques from the psychometric field to this line of research. The present study was conducted to examine the utility of applying such methods to animal research. Physiological responses to cold-restraint stress in 26 male rats were investigated using a factor analytic-multiple regression procedure. Nineteen behavioral and physiological measures obtained during open-field testing, motor activity monitoring, and passive avoidance learning were subjected to a principle components factor analysis. Five factors were extracted which reflected exploratory behavior, general activity level, metabolic rate, behavioral reactivity, and autonomic reactivity. The obtained factor scores were used to predict physiological responses to four hours of supine cold-restraint using a step-wise multiple regression procedure. General activity level was the best predictor of adrenal weight and temperature loss. Autonomic reactivity was the best predictor of ulcer incidence and severity. Applications of these statistical procedures are discussed.

Animals↗

PubMed1991

Restraint and stimulation of bed nucleus of the stria terminalis produce similar stress-like behaviors.

Restraint stress, electrical stimulation of the bed nucleus of the stria terminalis (BNST), and the combination of restraint stress and BNST stimulation were studied using a computerized animal activity monitoring system. Both restraint and the combination of restraint and BNST stimulation produced increases in locomotor, exploratory and stereotypic activity all of which returned to baseline within an hour while BNST stimulation alone also increased measurements of locomotor and exploratory behavior some of which remained elevated throughout the three-hour period of measurement. BNST stimulation also produced vigorous escape behavior and biting which were not seen with restraint alone. Thus electrical stimulation of BNST produces behavior which is qualitatively similar to the behavior produced by stress but differs in time course.

Animals↗

PubMed1997

GABAergic drugs and socio-sexual behavior.

To elucidate the role of GABA in the control of sexual behavior, the effects of the GABA(A) agonist 4,5,6,7-tetrahydroisoxazolo[5,4c]-pyridin-3-ol (THIP), the GABA transaminase inhibitors sodium valproate and gamma-acetylen-GABA (GAG), and the GABA synthesis inhibitors isoniazide and deoxypyridoxine were evaluated in sexual behavior, exploration, and sociosexual interactions with a receptive female or a castrated male. Furthermore, to discriminate possible general inhibitory effects from those specific to sexual behavior, the doses of the drugs that produced a significant inhibition of copulation were tested in a free drinking procedure. THIP (16 mg/kg), sodium valproate (400 mg/kg), GAG (100 mg/kg), and deoxypyridoxine (400 mg/kg) produced a strong inhibition of sexual behavior. The percentage of animals displaying mounts and intromissions as well as the mean number of mounts and intromissions were significantly reduced. Sociosexual interactions with a receptive female or a castrated male and exploratory behaviors were also reduced. The most consistent effects observed were reductions in sniffing, self-grooming, and rearing. Drinking behavior was significantly reduced in doses that inhibited sexual behavior. These results further support the hypothesis that altered GABAergic neurotransmission produces reduced sensitivity to environmental stimuli and thereby inhibits sexual and drinking behavior in a nonspecific way.

Animals↗

PubMed1981

[Effects of bilateral mammillary bodies destruction on lever pressing for food reward in the rabbit (author's transl)].

Effects for continuous reinforcement (CRF) learning and differential reinforcement of low rate (DRL) learning for food in the rabbit by bilateral mammillary bodies destruction were examined with the Skinner box. There was no marked changes in general behavior, except a tendency to freezing by a sign of somebody and sounds. In CRF learning a delay in the start of bar pressing was thought to be due to a decrease in exploratory behavior and a decrease of the number of bar pressing may be due either to a delay of adaptation to a new environment, or to an impediment of learning by the decrease in rewarding effects. The acquisition of DRL learning was affected, but the retention of that was not. DRL learning has been generally remarked to be chiefly consisted of motivation and temporal discrimination. In our study, however, there was no remarkable changes in motivation itself and temporal discrimination was not affected at all. It was concluded that the impediment of acquisition depended upon a general decrease in cerebral rewarding effects.

Animals↗

PubMed1995

Nonlinear dynamical patterns as personality theory for neurobiology and psychiatry.

ADVANCES in the theory of nonlinear differential equations and their statistical representations have yielded a powerful, qualitatively descriptive yet quantitative language that captures characteristic patterns of behavior (what the psychoanalyst Roy Schafer calls "continuity, coherence, and consistency of action") that has begun to influence studies of complex systems in motion as diverse in specifics as signatory patterns of discharge of neurochemically defined single neurons and the dynamical structures characteristic of a particular composer's music. What might be called personality theories of neurobiological dynamics have arisen to replace neurobiological theories of personality. It is in this way that rigorously proven and powerful general mathematical insights have changed the face of determinism in research in brain and behavior. Two examples: (1) Very complicated looking behavior of neurobiological forced-dissipative (expanding and contracting) systems over time take place on low dimensional abstract surfaces on which only a few underlying abstract parameters control the action. (2) Independent of specific details (chemical, electrical, and/or behavioral), there exist a relatively few fundamental categories of behavior in time and transitions, among them a property called universality. Results from this new theoretical, in contrast with experimental, reductionism yield analogies with and new approaches to historically important dynamic ideas about personality and character patterns that are equally relevant to micro and macrocomplex systems such as neural membrane receptor proteins and individual personality styles. Research findings achieved over the past decade and a half in our laboratory and others in neurochemistry, neurophysiology, and animal and human behavior, as well as the results of a new demonstration experiment involving the prediction of dynamical category membership from abstract expressive motion in humans, are used to exemplify this use of a quantitative dynamic category theory across disciplinary levels in brain and behavior. Multiple measures of complexity adapted from current research in the statistical properties of chaos on unobtrusively observed and reconstructed orbits on the computer screen made by non-premorbid subjects executing content-free, computer-game-like tasks with a mouse, were used to reliably differentiate the "signatures" of two Axis II diagnoses as established using SCID-II criteria. Whereas the techniques of nonlinear systems have achieved some success in quantifying and stimulating the dynamical styles of relatively local phenomena such as the spontaneous behavior of neuronal membrane conductances, single neurons, neural networks, and field electrical events, we think that the real power of these techniques lies in their quantitative description and statistical prediction of global patterns of behavior of entire systems. For example, since the late 1970s our work has shown that these measures could be used to discriminate categories of drug action and dose when applied to patterns of rat exploratory behavior in space and time. The combination of abstract generality and quantitative precision of these methods suggests their usefulness as a cross-disciplinary language for fields like psychiatry that deal with complicated behavior of both neurobiological elements and "the whole person."

Behavior↗

PubMed1991

Naloxone enhances epileptogenic and behavioral effects of pentazocine in rats.

Eight groups of six rats were either injected with saline, pentazocine, naloxone, or a combination of pentazocine and naloxone. Studied were the effects on EEG and behavior. It was found that pentazocine induced epileptic seizures in a dose-dependent fashion. In addition, similar behavioral changes were present after all three doses of pentazocine. High doses of naloxone did not cause epilepsy and affected behavior only slightly. Seizures induced by pentazocine were not antagonized by the opiate antagonist naloxone, but were facilitated after the combination of a noneffective dose of pentazocine and a noneffective dose of naloxone. In addition, exploratory behavior was facilitated by the combination of pentazocine and naloxone. It seems that both an opiate and a nonopiate system are involved in this type of epilepsy and in this type of behavior.

Animals↗

PubMedDate not supplied

Peptidergic transmission in the brain. VI. Behavioral consequences of central activation.

Having described a peptidergic transmitter system in the rat brain, we now begin to evaluate its behavioral function. We stimulated cell bodies in the medial amygdaloid nucleus (AME) with indwelling bilateral electrodes. These cell bodies contain a vasopressin-like peptide and send fibers to the hippocampus where the peptide is released upon stimulation. There the peptide inhibits hippocampal output in the awake rat just as it does in the anesthetized rat and in the rat brain slice. The stimulation reorganizes behavior with the same latency and duration as the hippocampal effect. For about 15-20 minutes after the brief stimulus, rats remain motionless with eyes wide open. This "freezing" state is punctuated by episodes of exploratory behavior. The stimulus appears to have a positive affective quality. Review of the literature in light of the present results indicates a probable role for this peptidergic system in the generation of sexual behavior in male rats.

Amygdala↗

PubMed2002

Masculine sexual behavior features in the Flinders sensitive and resistant line rats.

The Flinders sensitive (FSL) and resistant (FRL) lines of rats have been selectively bred for their differences in cholinergic sensitivity. The FSL rats display hypersensitive responses to agonists of muscarinic receptors. In addition, the FSL rats display behavioral alterations that support the notion that this strain could be useful as an animal model of depression. These abnormalities include increase in rapid eye movement sleep, decrease of saccharin consumption after stress, and reduced exploratory behavior in a novel open field. On the other hand, sexual behavior is a pleasure-seeking behavior that should be altered in a mood disorder characterized by anhedonia. In the present study, spontaneous masculine sexual behavior features were analyzed, both during 30-min tests as well as during a satiety test. Results showed that, compared to outbred Sprague-Dawley (SD) rats, both the FSL and the FRL rats displayed some behavioral impairment, like a marked decrease of the ejaculatory frequency. During the satiety tests, both the FSL and the FRL rats became exhausted sooner than their SD controls. In addition to considering the present results in terms of alterations in specific neurotransmitter systems, endogamy is proposed as a possible source of the behavioral alterations.

Animals↗

PubMed1997

Effect of gamma irradiation on the behavioral properties of crotoxin.

Crotoxin has been detoxified with gamma radiation in order to improve crotalic antiserum production. Nevertheless, present knowledge of the biological characteristics of irradiated crotoxin is insufficient to propose it as an immunizing agent. Crotoxin is known to increase the emotional state of rats and to decrease their exploratory behavior (Moreira EG, Nascimento N, Rosa GJM, Rogero JR and Vassilieff VS (1996) Brazilian Journal of Medical and Biological Research, 29: 629-632). Therefore, we decided 1) to evaluate the effects of crotoxin in the social interaction test, which has been widely used for the evaluation of anxiogenic drugs, and 2) to determine if irradiated crotoxin induces behavioral alterations similar to those of crotoxin in the social interaction, open-field and hole-board tests. Male Wistar rats (180-220 g) were used. Crotoxin (100, 250, and 500 micrograms/kg) was injected intraperitoneally 2 h before the social interaction test. Similarly, irradiated crotoxin (2000 Gy gamma radiation from a 60Co source) was administered at the doses of 100, 250, and 500 micrograms/kg for the hole-board test, and at the doses of 1000 and 2500 micrograms/kg for the open-field and social interaction tests. ANOVA complemented with the Dunnett test was used for statistical analysis (P < 0.05). Crotoxin decreased the social interaction time(s) at the doses of 100, 250 and 500 micrograms/kg (means +/- SEM) from 51.6 +/- 4.4 to 32.6 +/- 3.7, 28.0 +/- 3.6 and 31.6 +/- 4.4, respectively. Irradiated crotoxin did not induce behavioral alterations. These results indicate that 1) crotoxin may be an anxiogenic compound, and 2) in contrast to crotoxin, irradiated crotoxin was unable to induce behavioral alterations, which makes it a promising compound for the production of crotalic antiserum.

Animals↗

PubMed1986

Hippocampal responses evoked by tooth pulp and acoustic stimulation: depth profiles and effect of behavior.

Averaged evoked potentials and unitary discharges in response to tooth pulp and acoustic click stimuli were recorded from the hippocampus of freely moving rats. The spatial distribution of evoked field responses to tooth pulp stimulation and acoustic clicks were identical. Averaged evoked potentials consisted of a large negative deflection (N1) preceded by a small positive potential (P1). The shortest latency N1 in response to tooth pulp stimulation was recorded from the middle third of the dentate molecular layer and the outer portion of apical dendrites of CA3 (27 ms). The peak latency of N1 was significantly longer (34 ms) in the stratum radiatum of CA1. Laminar profiles of N1 in the dentate gyrus and CA3 were similar to that evoked by electrical stimulation of the medial entorhinal afferents; in CA1 the depth profiles of the potentials were similar to the response profile evoked by the Schaffer collaterals. Largest amplitude P1 was obtained from above the pyramidal layer of CA1 and the hilus. Both sensory modalities were able to modify the discharge rate of neurons in all hippocampal regions. The amplitude of evoked field potentials and cellular responses were dependent upon both the ongoing behavior of the animal and the nature of its response to the stimulus. The largest amplitude evoked potentials were recorded during immobility and slow wave sleep. On the other hand, virtually no potentials were obtained during exploratory behaviors associated with theta EEG activity. The findings indicate that information about sensory stimuli can reach the hippocampus by two distinctive pathways: a short latency inhibitory input via the fimbria-fornix and a longer latency path via the entorhinal cortex. It is suggested that neuronal mechanisms involved in theta EEG block the sequential activation of the unidirectional entorhinal-hippocampal circuitry.

Afferent Pathways↗

PubMed2005

The terrestrial Gastropoda Megalobulimus abbreviatus as a useful model for nociceptive experiments: effects of morphine and naloxone on thermal avoidance behavior.

We describe the behavior of the snail Megalobulimus abbreviatus upon receiving thermal stimuli and the effects of pretreatment with morphine and naloxone on behavior after a thermal stimulus, in order to establish a useful model for nociceptive experiments. Snails submitted to non-functional (22 degrees C) and non-thermal hot-plate stress (30 degrees C) only displayed exploratory behavior. However, the animals submitted to a thermal stimulus (50 degrees C) displayed biphasic avoidance behavior. Latency was measured from the time the animal was placed on the hot plate to the time when the animal lifted the head-foot complex 1 cm from the substrate, indicating aversive thermal behavior. Other animals were pretreated with morphine (5, 10, 20 mg/kg) or naloxone (2.5, 5.0, 7.5 mg/kg) 15 min prior to receiving a thermal stimulus (50 degrees C; N = 9 in each group). The results (means +/- SD) showed an extremely significant difference in response latency between the group treated with 20 mg/kg morphine (63.18 +/- 14.47 s) and the other experimental groups (P < 0.001). With 2.5 mg/kg (16.26 +/- 3.19 s), 5.0 mg/kg (11.53 +/- 1.64 s) and 7.5 mg/kg naloxone (7.38 +/- 1.6 s), there was a significant, not dose-dependent decrease in latency compared to the control (33.44 +/- 8.53 s) and saline groups (29.1 +/- 9.91 s). No statistically significant difference was found between the naloxone-treated groups. With naloxone plus morphine, there was a significant decrease in latency when compared to all other groups (minimum 64% in the saline group and maximum 83.2% decrease in the morphine group). These results provide evidence of the involvement of endogenous opioid peptides in the control of thermal withdrawal behavior in this snail, and reveal a stereotyped and reproducible avoidance behavior for this snail species, which could be studied in other pharmacological and neurophysiological studies.

Analgesics, Opioid↗

PubMed1995

Long-term behavioral effects of perinatal exposure to delta 9-tetrahydrocannabinol in rats: possible role of pituitary-adrenal axis.

This work evaluated motor behaviors in adult male and female rats exposed to delta 9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. The possibility that perinatal THC exposure induces sensitization to other drugs of abuse has also been addressed by evaluating morphine place preference conditioning (MPP) in the adult offspring. Maternal exposure to THC resulted in long-term effects on motor behaviors such as rearing, grooming and sniffing, in the adult offsprings of both sexes. Additionally, female offspring exposed to THC showed greater locomotor activity than controls, when measured using an actimeter. THC-exposed males exhibited an increased exploratory behavior in a plus-maze paradigm. When the adult animals were tested for MPP, THC-exposed offspring of both sexes exhibited an enhanced sensitivity to the rewarding effects of a moderate dose of morphine (350 micrograms/kg), an effect which was more marked in the males. These results showed that perinatal exposure to this psychoactive cannabinoid affected motor behaviors in the adult, suggesting a psychomotor activation very similar to that observed after gestational exposure to other drugs of abuse. A possible role of a THC-induced hypothalamus-pituitary-adrenal (HPA) axis activation was also evaluated in the present study. THC-exposed females exhibited higher levels of both corticotropin releasing factor (CRF-41) in the medial basal hypothalamus (MBH) and plasma corticosterone, whereas THC-exposed males showed the lower levels of both endocrine parameters. Since glucocorticoids are important modulators of both brain development, and adult brain function, these results indicate a possible role of HPA axis disturbances in the mediation of the behavioral effects described after perinatal THC exposure.

Adrenal Glands↗

PubMed1996

The effects of repeated administration of diazepam, MK-801 and CGP 37849 on rat behavior in two models of anxiety.

The effects of repeated administration of diazepam, MK-801 and CGP 37849 on rat behavior in the Vogel conflict test, and in the open field test of neophobia, were studied in rats. The drugs were given at doses active acutely, for 5 days, the last dose was administered 30 or 60 min prior to testing. It appeared that diazepam and MK-801 treated animals showed clear-cut signs of behavioral tolerance and motor sensitization, respectively. CGP 37849 was characterized by the best pharmacological profile, in that on repeated administration the drug not only retained its anxiolytic-like potency in the Vogel test, but even enhanced rat exploratory behavior in a new environment, independently of changes in animal motor activity. Repeated injections of the examined agents did not cause any significant modifications in monoamine levels and their turnover rates, in the striatum and limbic forebrain. It is concluded that the new class of competitive NMDA receptor antagonists, exemplified by CGP 37849, is the most promising candidate for clinical trials in anxiety disorders.

2-Amino-5-phosphonovalerate↗

PubMed1985

Pharmacological alleviation of cholinergic lesion induced memory deficits in rats.

The cholinergic cells of the nucleus basalis of Meynert (nbM) have recently been found to degenerate in Alzheimer's disease and are thought to be at least partly responsible for the cognitive deficits which are characteristic of this disease. These experiments explored the behavioral effects of bilateral excitotoxic lesions of the nbM in adult rats. The first experiment showed that nbM lesions lead to a substantial deficit in the 24 hour retention of the habituation to a novel environment without affecting general exploratory behavior. The second experiment showed that this retention deficit is a general phenomenon reflected in the 72 hour retention of a one trial passive avoidance task. These retention deficits could be reversed by the postacquisition administration of the acetylcholinesterase inhibitor, physostigmine. These results support the hypothesis that central cholinergic systems are involved in the retention of learned responses, and suggest that cholinergic lesion induced retention deficits can be reversed by pharmacological means.

Alzheimer Disease↗

PubMed1998

L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns.

L1 is a neural cell adhesion molecule mainly involved in axon guidance and neuronal migration during brain development. Mutations in the human L1 gene give rise to a complex clinical picture, with mental retardation, neurologic abnormalities and a variable degree of hydrocephalus. Recently, a transgenic mouse model with a targeted null mutation in the L1 gene was generated. These knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have performed further studies of these KO mice including magnetic resonance imaging of the brain, neuropathological analysis and behavioral testing. The ventricular system was shown to be abnormal with dilatation of the lateral ventricles and the 4th ventricle, and an altered shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the KO mice is hypoplastic. Their exploratory behavior is characterized by stereotype peripheral circling reminiscent of that of rodents with induced cerebellar lesions.

Animals↗

PubMed1989

Substantia nigra as a site of origin of dopamine-dependent motor syndromes induced by stimulation of mu and delta opioid receptors.

Opioid agonists having different affinity for delta and mu receptors were injected bilaterally in the substantia nigra (SN) of rats. The selective agonist of mu receptors N-MePhe3,-D-Pro4 morphiceptin (PLO 17) produced a stereotyped behavior characterized by stereotyped sniffing and gnawing antagonized by the irreversible antagonist of mu receptors beta-funaltrexamine. In contrast, bilateral intranigral injection of the selective delta agonist D-Pen2,D-Pen5 enkephalin (DPDPE) elicited dose-dependent exploratory behavior and rearing but failed to produce gnawing. The behavioral syndrome induced by DPDPE was significantly reduced by the selective delta antagonist ICI 174,864. Naloxine, a non-selective opioid antagonist, antagonized the effects of both compounds. SCH 23390 and haloperidol, two antagonists of dopaminergic D1 and D2 receptors, respectively, blocked the effects of PLO 17 and DPDPE. The results indicate that stimulation of specific opioid receptor types in the SN elicits specific behavioral syndromes and suggest that the SN might be the site of origin of certain items of the behavioral syndrome evoked by systemic opiates. These items might be mediated by activation of dopaminergic neurons of the ventral mesencephalon.

Animals↗

PubMedDate not supplied

[Changes in the behavior and EEG of rats administered penicillin and a physiological solution into the amygdalar basal nuclei].

Three weeks after implantation of the electrodes for EEG recording, hyperactivation of the basal nucleus of rat's amygdala was produced by a local injection of penicillin (0.5 mcl, 1% solution). Saline injection of the same volume served as control. The hyperactivation of the amygdala resulted in a long-lasting (at least for 3 weeks) increase in the locomotor activity against the background and deficit in exploratory behavior and rise of the level of anxiety and fear. The behavioral changes were accompanied by a long-term disruption of the hippocampal theta rhythm, appearance and slowing of the immobility-related high-voltage spindles, and increase in the EEG dominant frequency in the state of emotional tension. Saline injection led to a short-time (up to 1 week) decrease in locomotor and exploratory activity and increase in anxiety. These phenomena were accompanied by a short-time disruption of the theta rhythm and appearance of the 10-13-Hz oscillations characteristic for the state of emotional tension.

Amygdala↗

PubMed2006

Febrile convulsions in developing rats induce a hyperanxious phenotype later in life.

Exposure of rodent pups to hyperthermia constitutes one of the best known models of febrile seizures. Studies designed to evaluate the behavioral impact of heat-induced convulsions (HCs) have focused mainly on hippocampus-dependent tasks and produced rather conflicting results. In this study, we assessed, in detail, developmental milestones, emotional behavior, and cognitive performance in animals submitted to HCs on Postnatal Day 10. There was no alteration in the acquisition of neurological reflexes, but there was an anticipation of eye opening in animals exposed to hyperthermia. As adults, the locomotor and exploratory behavior of these rats was unaffected. Interestingly, animals exposed to hyperthermia displayed signs of increased anxiety in the elevated-plus maze, although these signs were not associated with increased susceptibility to depression-like behavior. Additionally, we failed to observe impairments in spatial and working memory tasks. In conclusion, HCs at a particular period of neurodevelopment determine a hyperanxious phenotype later in life.

Animals↗