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PubMed1987

The effects of repeated doses of ethanol on exploration and its habituation.

The effects of ethanol (0.8-2.4 g/kg) on exploratory behavior and its habituation were investigated by testing DBA/2 mice in a holeboard apparatus. Mice familiar with the holeboard had lower levels of exploration than animals with no previous experience in the apparatus. If the animals received ethanol during their first exposure to the holeboard they did not show the same degree of habituation. Ethanol (0.8 g/kg) increased the exploration of animals naive to the holeboard, but failed significantly to increase the exploration of animals familiar with the apparatus. An increase in locomotor activity was observed following treatment with ethanol (2.4 g/kg). This was potentiated if animals received a single treatment with ethanol 3 days earlier, but only if they were tested in the apparatus following the initial treatment. These results have important implications for the design of experiments investigating tolerance and sensitization to ethanol's effects on locomotor activity and exploration.

Animals↗
PubMed1998

Unilateral hippocampal lesions in newborn and adult rats: effects on spatial memory and BDNF gene expression.

Subcortical damage at birth often produces more severe deficits than similar lesions in an adult. In the present study, effects of unilateral electrolytic hippocampal ablations made on postnatal day 1 or in 3-month-old adult rats, were compared. Exploratory behavior and spatial navigation in the Morris water maze (MWM) were assessed 8 and 20 weeks after hippocampal damage. Rats with neonatal damage did not respond to novelty in the environment and did not learn to find the hidden platform in the MWM. Rats lesioned as adults did learn the water maze task, but slower than controls. We hypothesized that behavioral deficits observed in rats lesioned at birth, may be due, in part, to neurochemical dysfunction of the contralateral hippocampus. Specifically, cholinergic and GABAergic neurotransmission were assessed by measuring choline-acetyltransferase (ChAT) and GABAdecarboxylase (GAD) activity. In addition, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA levels were assayed in the remaining (contralateral) hippocampus. Of these molecules, only BDNF gene expression was significantly reduced (by 30%) at 8 and 20 weeks after neonatal and adult unilateral ablation. The similar reduction in BDNF mRNA in both treatment groups does not correspond with the lesion's differential effect on memory function. However, the more severe learning impairment after neonatal lesion may reflect increased dependence on trophins during development.

Aging↗
PubMed2000

Habituation of activity in an open field: A survey of inbred strains and F1 hybrids.

To determine if there is genetic variability in habituation of activity in an open field, we examined a number of inbred strains and F1 hybrids. Using 5-min exposures to a dark open field, we measured changes in exploratory behavior over 3 consecutive days in 129S3/SvImJ, A/J, BALB/ cByJ, C3H/HeJ, C57BL/6J, CBA/J, DBA/2J, FVB/NJ, (B6 x 129)F1/J, and (B6 x C3H) F1/J male and female mice. Strain differences in open-field activity and in habituation were evident. Some of the strain differences were further modified by sex. The strains and F1's could be separated into groups that increased, decreased, or did not modify their activities across testing sessions. In a second study, the effects of altering the floor surface on habituation were examined in male 129S3/SvImJ, C57BL/6J, DBA/2J, and (B6 x 129)F1/J mice. When the floor was altered after 3 consecutive days of habituation, increased activity levels were evident. There were strain differences in the responsiveness to the changes in the floor. These results confirm a genetic role in intersession habituation to an open field.

Animals↗
PubMed2004

Prospective investigation of stress inoculation in young monkeys.

BACKGROUND: Retrospective studies in humans have identified characteristics that promote stress resistance, including childhood exposure to moderately stressful events (ie, stress inoculation). OBJECTIVE: Because of limited opportunities for prospective studies in children, we tested whether exposure to moderate stress early in life produces later stress resistance in a primate model. DESIGN AND MAIN OUTCOME MEASURES: Twenty squirrel monkeys were randomized to intermittent stress inoculation (IS; n = 11) or a nonstress control condition (NS; n = 9) from postnatal weeks 17 to 27. At postnatal week 35, each mother-offspring dyad underwent testing in a moderately stressful novel environment for inferential measures of offspring anxiety (ie, maternal clinging, mother-offspring interactions, object exploration, and food consumption) and stress hormone concentrations (corticotropin [ACTH] and cortisol). At postnatal week 50, after acclimation to an initially stressful wire-mesh box attached to the home cage, independent young monkeys underwent testing for inferential measures of anxiety (ie, voluntary exploration and play) in the box. RESULTS: In the novel environment test, IS compared with NS offspring demonstrated diminished anxiety as measured by decreased maternal clinging (P =.02), enhanced exploratory behavior (P =.005), and increased food consumption (P =.02). Mothers of IS offspring accommodated offspring-initiated exploration (P =.009) and served as a secure base more often compared with NS mothers (P =.047). Compared with NS offspring, IS offspring had lower basal plasma ACTH (P =.001) and cortisol (P =.001) concentrations and lower corticotropin (P =.04) and cortisol (P =.03) concentrations after stress. In the subsequent home-cage wire-box test, IS offspring demonstrated enhanced exploratory (P<.001) and play (P =.008) behaviors compared with NS offspring. CONCLUSIONS: These results provide the first prospective evidence that moderately stressful early experiences strengthen socioemotional and neuroendocrine resistance to subsequent stressors. This preclinical model offers essential opportunities to improve our understanding and enhance prevention of human stress-related psychiatric disorders by elucidating the etiology and neurobiology of stress resistance.

Adaptation, Physiological↗
PubMed2004

Insular dopamine D2 receptors and novelty seeking personality in Parkinson's disease.

Novelty seeking is a temperament trait characterized by impulsiveness and exploratory behavior. Dopamine has been suggested to be the primary neurotransmitter modulator of novelty seeking, and in young healthy subjects, a correlation between increased novelty seeking and decreased insular cortical dopamine D2 receptor availability has been reported. The proposed link between dopamine deficiency and reduction in novelty seeking in Parkinson's disease is controversial. The present study examined whether a link between insular D2 receptor availability and novelty seeking can be replicated in Parkinson's disease patients. [11C]FLB 457 positron emission tomography imaging was carried out in 28 patients with Parkinson's disease, and the data were analyzed using voxel-based statistical analysis. The results demonstrated a negative correlation between the novelty seeking score and the dopamine D2 availability bilaterally in the insular cortex (corrected P=0.001; r=-0.74 [right hemisphere]; r=-0.66 [left hemisphere]). The results provide further support for a relationship between novelty seeking and insular D2 receptors. They indicate that the association is cross-cultural, independent of age, and unaffected by dopaminergic degeneration.

Aged↗
PubMed1986

On the use of some multivariate statistical methods in pharmacological research.

Using an interaction experiment with apomorphine and scopolamine effects on exploratory behavior as an illustrative example, four multivariate statistical methods are described and compared with univariate statistical methods, with respect to their utility in pharmacological research. The utility of multivariate analysis of variance and Hotelling's T2 test is compared with univariate analysis of variance and Student's t-test. A novel use of principal component analysis is reported. This latter method transfers knowledge about the dose-response pattern of an agonist to subsequent interaction experiments involving the agonist and putative antagonists. The procedure considerably increases the sensitivity of the statistical analysis and reduces the risk for spurious results (statistical type I errors). Finally, some possibilities of a recently developed method for modeling with latent variables, the partial least squares method, are explored. It is demonstrated by the example how the interaction between apomorphine and scopolamine can be decomposed into one apomorphine-related pattern unaffected by scopolamine, one scopolamine-related pattern sensitive to apomorphine, and one interaction pattern. The similarities and differences between principal components and partial least squares analyses are also discussed.

Animals↗
PubMed1986

Comparison of motor depressant effects of caerulein and N-propylnorapomorphine in mice.

The motor depressant effects of caerulein and N-propylnorapomorphine (NPA) were compared in male mice. Caerulein (1-50 micrograms/kg SC) in a dose dependent manner depressed the exploratory activity, whereas NPA in lower doses (0.5-10 micrograms/kg SC) decreased the motor activity, but in higher doses (over 50 micrograms/kg) had stimulating effect on the exploratory behavior. In mice selected according to their motor response after administration of 100 micrograms/kg NPA to weak and strong responders, the low dose of NPA (1 microgram/kg) similarly suppressed motor activity in both selected groups, while the effect of caerulein (2 micrograms/kg) was apparently higher in weak responders. Destruction of catecholaminergic terminals by 6-hydroxydopamine (60 micrograms ICV) reversed completely the motor depressant effect of NPA, whereas degeneration of serotoninergic terminals (5,7-dihydroxytryptamine 60 micrograms ICV or p-chloroamphetamine 2 X 15 mg/kg IP) enhanced the sedative effect of NPA. The motor depressant effect of caerulein remained unchanged after lesions of monoaminergic terminals in forebrain. Subchronic haloperidol (0.25 mg/kg IP, twice daily during 14 days) treatment, reducing significantly the density of high-affinity dopamine2- and serotonin2-receptors, decreased the motor depressant action of caerulein. It is possible that motor depressant effect of caerulein, differently from the action of NPA, is mediated through the high-affinity dopamine2-receptors and in lesser extent through the high-affinity serotonin2-receptors.

5,7-Dihydroxytryptamine↗
PubMed1993

Neuroendocrine and neurochemical responses to novelty stress in young and old male F344 rats: effects of d-fenfluramine treatment.

To understand some of the mechanisms underlying the neuroendocrine and neurochemical changes associated with aging, we administered the serotonin [5-hydroxytryptamine (5-HT)] releaser and reuptake inhibitor d-fenfluramine (d-FEN; 0.0, 0.2, or 0.6 mg/kg/day, p.o) for 30-38 days to young (4 months) and old (22 months) F344 male rats. Rats were stressed by placement into a novel open field (OF) for 20 min before sacrifice. Control animals were sacrificed immediately upon removal from their home cage (HC). Old rats exhibited less (p < 0.05) exploratory behavior than young rats, which was not altered by treatment with d-FEN. Old HC rats also had higher (p < 0.05) basal plasma levels of adrenocorticotropic hormone (ACTH) and prolactin (PRL) than young HC rats. Old OF rats showed higher (p < 0.05) levels of ACTH and corticosterone (CORT) than young OF animals. A stress-induced increase in PRL secretion was not observed in old rats. Subchronic low-dose d-FEN normalized the enhanced ACTH and CORT responses of old animals to novelty. In addition to these endocrine changes, stress-induced increases in medial frontal cortex (MFC) dopamine (DA) and norepinephrine (NE) turnover also were observed. The increase in NE turnover was greater (p < 0.01) in old than in young rats. d-FEN treatment blocked the stress-induced increase in MFC NE but not MFC DA turnover in both young and old rats. These data support a role for 5-HT and/or NE in some age-related neuroendocrine perturbations and suggest that increased 5-HT neurotransmission can normalize the hyperactivation of the hypothalamo-pituitary-adrenal axis of old male rats.

Adrenocorticotropic Hormone↗
PubMed1998

Facilitation of olfactory recognition by lateral entorhinal cortex lesion in rats.

An original olfactory recognition task was developed in order to examine the effect of lateral entorhinal cortex (LEC) lesion on olfactory mnesic processes. The task was based on the spontaneous exploratory behavior of rats toward odor sources. It consisted of a learning phase during which an odor was presented twice and in a recognition test, during which the same odor plus a new one was presented. The time rats spent sniffing the odor sources was measured. Olfactory recognition was identified by a short investigatory duration for the familiar odor as compared to a normal investigatory duration for the new odor during the test. The first three experiments aimed to validate the procedure. Experiment 1 was designed to show the decay of investigatory behavior caused by repeated exposure of the rats to one odor. Experiment 2 showed that normal rats display recognition when a short (5 or 40 min) pre-test delay was used, but not when a long pre-test delay (120 min) was used. Experiment 3 showed that FG7142, a well-known promnesic drug, enhanced the performance of the rats in this test as it allowed recognition at longer pre-test delays. The last experiment aimed at testing the effects of aspirative lesion of the LEC. Therefore, LEC-lesioned and sham-lesioned rats were submitted to variable pre-test delays. The experiment showed that an entorhinal lesion did not produce an impairment, but on the contrary facilitated olfactory recognition, as lesioned rats displayed recognition for delays at which sham-operated rats did not. These results show that LEC lesion apparently prolongs the duration of the olfactory mnesic trace. This effect might result from a modification of the functioning of structures innervated by the LEC. In this regard, it is noteworthy that LEC lesion produced a sprouting of septo-hippocampal fibers in the dentate gyrus of the hippocampus as assessed by acetylcholinesterase staining. Although the functional significance of this regrowth is not fully understood, the possible role of this sprouting should be considered.

Animals↗
PubMed1995

The transfer of rats from a familiar to a novel environment prolongs the increase of extracellular dopamine efflux induced by CCK8 in the posterior nucleus accumbens.

The effects of cholecystokinin octapeptide (CCK8) on extracellular dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were measured in the nucleus accumbens (N. Acc.). The experiments were carried out using in vivo microdialysis in awake rats submitted, or not, to a novel environment, the four-hole box. The exploratory behavior of the animals was studied concurrently in these boxes and in the elevated plus maze. Without CCK8 treatment, the transfer of animals from their home cages to the four-hole box induced a transient increase in DA efflux and also tended to increase its metabolites in the posterior N. Acc. In rats placed in a familiar environment, the administration of 25 pmol of CCK8 in this region immediately enhanced DA release, with levels rapidly returning to normal at the end of the perfusion. In contrast, this treatment produced a longer effect in rats transferred to the four-hole box, since the DA efflux was still increased 80 min after the removal of CCK8. The intra-accumbal administration of CCK8 induced a hypoexploration in the four-hole box. Moreover, an anxiogenic-like effect of CCK8 was found in the elevated plus maze, only in rats submitted to a novel environment (four-hole box). These data show that (1) the postero-accumbens DA neurons can be activated by environmental changes and (2) that the intensity of the CCK8 effects on extracellular DA levels and on anxiety-like responses seems to depend on the activity of these neurons previous to CCK8 treatment. The prolonged DA release induced by CCK8 in animals placed in a new situation could correspond to a biochemical anticipation preparing them to react when faced by another stimulus.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

The dynamics of long-term exploration in the rat. Part I. A phase-plane analysis of the relationship between location and velocity.

Rat exploratory behavior consists of regular excursions into the environment from a preferred place termed a home base. A phase plane representation of excursions reveals a geometrical pattern that changes during exploration in both shape and size. We first show that with time and repeated exposures to the same large environment there is a gradual increase in the length of excursions; each rat has its own characteristic length of excursions; but all rats share a similar rate of excursion growth. As in our experimental setup the rats perform increasingly longer paths from one location, while locomoting back and forth along the walls of the arena, exposure is more extensive at the proximal part of the route, and less at the distal part. We consequently show that the rat's velocity pattern changes concurrently with the increase in excursion length, and in correlation with the level of exposure (familiarity) to places. The primitive velocity pattern consists of slow progression while moving away from base and fast progression while returning to it. During exposure the asymmetry in velocity is inverted. The inversion spreads across successive excursions from the home base outwards. The rate of spread of this inversion is higher than the rate of increase in excursion length, and is similar across rats. Because it spreads more rapidly than the increase in excursion length, the global shape of the excursion trajectory changes. The dynamics of excursion shape share similar properties with the dynamics of excursion length. Both might reflect the same intrinsic constraints on the amount of novelty that a rat can handle per excursion.

Animals↗
PubMed1988

Dopamine mediated behavior and GABA influence.

The possibility of interactions between GABA and dopaminergic central nervous mechanisms in the expression of spontaneous behavior was investigated using the behavior pattern shown by male rats in an exploratory test situation. The present study corroborates the facilitatory action of low doses of the dopamine agonist apomorphine on the investigative activity element of the male rats exploratory behavior pattern, as shown previously. In addition it was found that the GABA agonist baclofen in different doses (1.2-4.8 mg/kg IP) selectively increased this activity. Pretreatment with a submaximal dose of baclofen (1.2 mg/kg) potentiated the effect of apomorphine (25 micrograms/kg), indicating that baclofen has the same effect on behavior as presynaptically active dopamine agonists. Thus GABA mechanisms might influence dopamine mediated behavior. The investigative activity which previously has been considered to reflect the adaptive state of an animal is suggested to be influenced by a changed activity in GABA neurons, DA neurons or an interaction between these two systems in the various brain structures involved in the expression of this behavior.

Animals↗
PubMed2006

Recurrence plot analyses suggest a novel reference system involved in newborn spontaneous movements.

The movements of newborns have been thoroughly studied in terms of reflexes, muscle synergies, leg coordination, and target-directed arm/hand movements. Since these approaches have concentrated mainly on separate accomplishments, there has remained a clear need for more integrated investigations. Here, we report an inquiry in which we explicitly concentrated on taking such a perspective and, additionally, were guided by the methodological concept of home base behavior, which Ilan Golani developed for studies of exploratory behavior in animals. Methods from nonlinear dynamics, such as symbolic dynamics and recurrence plot analyses of kinematic data received from audiovisual newborn recordings, yielded new insights into the spatial and temporal organization of limb movements. In the framework of home base behavior, our approach uncovered a novel reference system of spontaneous newborn movements.

Biomechanical Phenomena↗
PubMed1990

Behavioral effects of PCBs in mice.

A single i.p. administration to mice of Fenclor 54 (PCB) resulted in various behavioral deficits. PCB significantly reduced locomotor activity and exploratory behavior at dosages of 150 and 300 mg/kg. Dose dependent increased latencies were also found at the same dosages in the "traction test" while in the rota rod test the dosage of 300 mg/kg of PCB only caused a significant increase in mean number of falls off the rod. Furthermore daily dietary administration of PCB (1, 10, 100 ppm) to male mice during a 21-day isolation period was inversely proportional to the amount of aggressive behavior shown, and directly proportional to the amount of non-social behavior ("indifference"). This supports former findings reporting anti-androgenic like effects of PCBs.

Journal Article↗
PubMed1987

A genotype-dependent hippocampal dynorphinergic mechanism controls mouse exploration.

Following microinjections with two dilutions of anti-dynorphin B antiserum into the hippocampal CA3 region, adult male mice from the inbred strains DBA/2 and C57BL/6 were individually tested for various exploratory behaviors in a novel environment and compared to preimmune serum control animals. Treatment augmented vertically-oriented exploratory acts in strain DBA/2 and reduced the scores in strain C57BL/6 so that strain differences originally present between the controls were reversed or eliminated after antiserum. These opposite effects indicate that a hippocampal dynorphinergic mechanism is involved in the regulation of novelty-induced behavior in mice and that its modulatory function depends on the genotype. It is concluded that DBA/2 animals exposed to novelty, as compared to C57BL/6, are characterized by an over-release of hippocampal dynorphin B which is neutralized in part by small amounts of antibody.

Animals↗
PubMed1998

Influence of testosterone on some behavioral reactions of male immature rats.

The complicated reflex complexes on the basis of orientation exploratory-behavior, emotional state and pain reaction play an important role in the analisator activity of the brain cortex. The rate of inhibition of orientation-exploratory reactions shows the intensity of the inner inhibition. In a complex with other indicators it can characterize the intensity and the mobility of the basic nerve processes of the cortex. The role of the neurosteroids has not been studied sufficiently in this direction. The results of the present study show the role of testosterone in the regulation of the horizontal and vertical locomotor activity and the latent period of the pain reaction of male immature rats. They are part of an investigation on the role of neurosteroids in adaptive reactions. The indicator entropy of the behavior as a characteristic of the organization of the behavior of rats in an open field study together with the probability structure of the behavior was also used. Testosterone was found to inhibit the horizontal and vertical locomotor activity of rats and prolong the latent period of the pain reaction in the tail flick test. The effect of the neurosteroid was apparent 4 hours after injection and was maintained for 24 hours. It was concluded that testosterone might play a role in the regulation of the locomotor behavioral acts and of the pain reaction. Testosterone influences all the organization of the behavior, it decreases the entropy of the behavior which is connected with a precipitation of the process of inhibition of the exploratory activity and the emotion reactivity, simultaneously changing the dynamic of the behavioral entropy.

Animals↗
PubMedDate not supplied

[Effect of alpha-tryptophan on conditioning and behavior in rats with experimental pathology of the thyroid gland].

Effects of L-tryptophan on learning and behavior were studied in male rats with a deficit or excess of thyroid hormones. Learning was assessed in active avoidance paradigm, and behavior was estimated in the "open-field" test. It was found that L-tryptophan restored the capability of thyreoidectomized rats for acquisition and reproduction of the active avoidance reaction and increased the exploratory behavior of these rats in the open-field. In triiodothyronine treated rats, L-tryptophan eliminated a light stimulatory effects of thyroid hormones on the processes of formations and retention of the active avoidance reaction, increased the exploratory activity, but decreased grooming in the open-field.

Animals↗