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At least 19 recordsLinked to original sources
PubMed2005

Effects of experimental increases and decreases in thyroxine levels on the extent of cataleptic freezing reactions in rats.

Numerous clinical observations have provided evidence for a tight connection between impairments in the functions of the hypothalamo-hypophyseal-thyroid system and nervous and mental disorders. The aim of the present work was to compare the effects of experimental decreases and increases in blood thyroxine levels on the extents of two types of pathological freezing reaction in male Wistar rats--spontaneous catalepsy and catalepsy evoked by pinches at the nape of the neck (pinch-induced catalepsy). Chronic administration of the thyroxine synthesis inhibitor propylthiouracil (5 mg/kg/day for 28 days) significantly decreased the blood hormone level and sharply increased the proportion of animals showing spontaneous catalepsy and the immobility time, but had no effect on the extent of pinch-induced catalepsy. At the same time, chronic administration of thyroxine (0.1 mg/kg/day for 28 days), which produced significant increases in blood hormone levels, had no effect on the extent of spontaneous catalepsy but significantly increased the proportion of animals showing pinch-induced catalepsy and the duration of this type of catalepsy. It is concluded that both insufficiency and excess of thyroid hormones have cataleptogenic actions, but enhance different types of catalepsy.

Animals↗
PubMed2004

[Bipolar manifestation of cataleptic reactions in rats].

Selection of GC rats for the predisposition to cataleptic freezing has increased not only the frequency, intensity, and duration of freezing, but also the proportion of irritable or "nervous" rats with enhanced anxiety, defensive behavior with vocalization, jerky running, and jumpiness. An increased amplitude of the startle reflex is a correlate of this "nervousness." The results of the comparison of some behavioral characters in the nervous and freezing GC rats, as well as in F1 and F2 offspring from homogeneous crosses between nervous and freezing GC rats suggest that cataleptic freezing and nervousness are two poles of the same bipolar catatonic reaction. They have a common mechanism, with the alternative or preferential expression of one particular form of the reaction is determined by the external and internal environments or the set of modifier genes in the given individual.

Animals↗
PubMed2006

Selective breeding for catalepsy changes the distribution of microsatellite D13Mit76 alleles linked to the 5-HT serotonin receptor gene in mice.

Catalepsy (pronounced motor inhibition) is a natural defensive reaction against predator. Recently, the quantitative trait locus for catalepsy was mapped on mouse chromosome 13 near the 5-HT(1A) serotonin receptor gene. Here, the linkage between catalepsy and the 5-HT(1A) receptor gene was verified using breeding experiment. Selective breeding for high predisposition to catalepsy was started from backcross BC[CBA x (CBA x AKR)] generation between catalepsy-prone (CBA) and catalepsy-resistant (AKR) mouse strains. CBA and AKR strains also differed in the 5-HT(1A) receptor functional activity. A rapid increase of cataleptic percentage from 21.2% in the backcrosses to 71% in the third generation of selective breeding (S3) was shown. The fragment of chromosome 13 including the 5-HT(1A) receptor gene was marked with D13Mit76 microsatellite. Breeding for catalepsy increased the concentration of CBA-derived and decreased the concentration of AKR-derived alleles of microsatellite D13Mit76 in the S1 and S2. All mice of the S9 and S12 were homozygous for CBA-derived allele of D13Mit76 marker. Mice of the S12 showed CBA-like receptor activity. These findings indicate that selective breeding for behavior can involve selection of polymorphic variants of the 5-HT(1A) receptor gene.

Animals↗
PubMed2005

Cataleptic activity of the denatured venom of the social wasp Agelaia vicina (Hymenoptera, Vespidae) in Rattus norvegicus (Rodentia, Muridae).

Catalepsy is a state of immobility, commonly experienced by patients with chronic use of many antiparkisonism and neuroleptic drugs. Recently, catatonia has been considered as an evolutionary-based fear response. The cataleptogenic effects of the low molecular weight compounds from the venom of the social wasp A. vicina (AdAv) were reported in rodents. Intracerebroventricular injections of AdAv in highest dose reduced the locomotor activity of Wistar rats in the open field and induced ataxia and catalepsy within 10 min. This effect could be observed up to 30 min after injections. Lower doses of denatured venom injected in brain ventricles also reduced the locomotor activity of the rats but did not induce catalepsy. The cataleptic effects of the intracerebrally administered AdAv were antagonized by the peripheral (intraperitoneal) pretreatment with theophylline and ketamine. Moreover, the central effects of the AdAv were compared to those elicited by the neuroleptic drug haloperidol (intraperitoneally administered), whose cataleptic effects were also antagonized by theophylline and ketamine. However, the association of haloperidol and denatured venom was reverted by theophylline but not by ketamine. These findings suggest that A. vicina venom may affect neural substrates involved with catalepsy in the central nervous system.

Analysis of Variance↗
PubMed2006

Differential effect of testosterone and repetitive induction on cataleptic and dorsal immobility in mice.

In nature, many species under conditions of stress (e.g., predator attack, pups carried by the mother, mating) show immobility states called "immobility responses" (IRs), which are characterized by the complete absence of movement and a relative unresponsiveness. These IR states can be induced by several kinds of sensorial stimuli. Many brain neurotransmitters from diverse cerebral areas participate in the expression of IRs. Other factors are also involved in IRs, such as learning and hormones, but at present, there is not enough experimental support about these factors. Our purpose was to investigate whether the IRs are subject to sexual hormone modulation and to examine the possible relation to learning processes. We tested the effects of acute testosterone decanoate (30 mg/kg, s.c.) and repetitive induction of two IRs; cataleptic immobility (CAT) and dorsal immobility (DI). These were tested in mice of both sexes which were either gonadectomized or sham-treated. CAT and DI were measured before and then 1 and 5 h after testosterone injection. The results show a differential effect of the repetitive induction on CAT and DI. CAT was augmented with repetition, and DI was decreased. Sex differences of the effects of the acute testosterone treatment were observed. Sham and castrated male mice showed CAT potentiation; in contrast, DI was reduced albeit only in sham male mice. Sham and ovariectomized female mice were not affected by testosterone. These results support the hypothesis that there are multiple immobility systems that can be differentially modulated by brain regions associated with processes of learning.

Analysis of Variance↗
PubMed2005

Neural mechanisms of freezing and passive aversive behaviors.

Cues that predict aversive outcomes often produce marked inhibitions of behavior known as freezing, but it is unknown exactly what neural pathways cause this inhibition. The amygdala and bed nucleus of the stria terminalis, along with their projections to the periaqueductal gray, are strongly implicated in freezing, but it is not known how these structures inhibit motor output. The median raphe nucleus (MRN), which contains a major population of serotonin neurons, has also been implicated in freezing, but the serotonin neurons themselves do not seem to be involved, leaving it uncertain which neurons in this area promote freezing. Our recent work suggests that GABAergic neurons just lateral to the MRN, but not within the MRN, regulate freezing via projections to midbrain dopamine neurons. Because freezing pathways may control a variety of other passive aversive behaviors, their elucidation may help understand the mechanisms of addictions and compulsions, which involve a failure of aversive outcomes to inhibit behavior.

Amygdala↗
PubMed2005

Latent inhibition in the developing rat: an examination of context-specific effects.

Latent inhibition (LI) refers to the reduction in conditioned responding when the conditioned stimulus (CS) is preexposed prior to CS-unconditioned stimulus pairings. Experiment 1a demonstrated that preexposure to an odor CS prior to odor-shock pairings markedly reduced conditioned freezing in 25-day-old rats; however, this LI effect was observed only if odor preexposure and odor-shock pairings occurred in the same context (i.e., LI was context-specific at this age). The results of Experiment 1b showed that 18-day-olds also exhibited LI, but this effect was not context-specific at this age. In Experiment 2, rats were preexposed to the odor at 18 days of age and given odor-shock pairings at 25 days of age. These rats exhibited context-specific latent inhibition, suggesting that 18-day-old rats encoded the preexposure context. In Experiment 3, all parameters were identical to Experiment 2, with the exception that odor-shock pairings were given at approximately PN18 and testing occurred at approximately PN25. These rats exhibited latent inhibition at test, but this effect was not context-specific. The results of this study suggest that (a) PN18 rats can exhibit latent inhibition, and (b) the expression of context-specific latent inhibition depends on the age at which conditioning occurs.

Analysis of Variance↗
PubMed2006

Pharmacological activity of three commercial Hypericum perforatum preparations in mice.

St John's Wort (Hypericum perforatum) is the main herbal species used to treat depression. The products available on the pharmaceutical and dietary supplement markets are obtained by a variety of preparation processes and their pharmacological effects may differ significantly. The purpose of this study therefore was to investigate the effect of different St John's Wort commercial preparations available on the French market. Only one preparation gave significant results in the forced swimming test.

Animals↗
PubMed2005

Cortical GABAergic regulation of dopaminergic responses to psychological stress in the rat dorsolateral striatum.

The present study was undertaken to examine the possible involvement of cortical gamma-aminobutyric acid (GABA) neuronal mechanisms in the regional differences of dopamine (DA) response to psychological stress: contextual fear conditioning (CFC) in the rat prefrontal cortex (PFC) and dorsolateral striatum (DLS). Rats that received five footshocks (shock intensity, 0.5 mA; shock duration, 2 sec) were subjected to CFC and dynamic changes in DA and GABA in both PFC and DLS were examined using dual-probe microdialysis. Extracellular levels of DA in the PFC were enhanced during exposure to CFC, whereas the levels in the DLS were not affected by this stimulus. Extracellular levels of GABA in the PFC, but not in the DLS, were markedly enhanced by CFC. Freezing behavior observed during exposure to CFC was attenuated by the GABA(A) receptor antagonist bicuculline (10(-3) M), which was perfused into the PFC. Intracortical application of bicuculline (10(-3) M) furthermore caused sustained increases in DA levels in the DLS by CFC. These data suggest that cortical GABA(A) receptors contribute to modulation of DA release in the DLS in response to CFC. Thus, the GABAergic neuronal system in the PFC appears to play a key role in the regional differences of the DAergic response to psychological stress.

Analysis of Variance↗
PubMed2006

The cannabinoid receptor agonist WIN 55,212-2 facilitates the extinction of contextual fear memory and spatial memory in rats.

RATIONALE: Previous studies demonstrated that pharmacological blockade of CB1 cannabinoid receptors decreases the extinction of conditioned fear and spatial memory in rodents. However, the effects of CB1 cannabinoid receptor activation in this response remain unclear. OBJECTIVES: To evaluate the effects of the cannabinoid agonist WIN 55,212-2 (WIN) and the cannabinoid antagonist SR 147778 (SR) on the extinction of contextual fear memory in rats 24 h or 30 days after fear conditioning. METHODS: For fear conditioning, rats were placed in the conditioning chamber for 3 min and received a 1-s electric foot shock (1.5 mA). Retrieval testing consisted of a 3-min exposure to the conditioning chamber and extinction training consisted of successive 9-min exposures at 24-h intervals. Rats were also evaluated in the open field and water maze reversal task. RESULTS: The administration of SR (1.0 mg/kg, i.p.) and WIN (0.25 mg/kg, i.p.) before extinction training disrupted and facilitated, respectively, the extinction of 24 h contextual fear memory. These effects were not related to any disturbance in memory retrieval, unconditioned freezing expression, or locomotor activity. WIN (0.25 mg/kg, i.p.) also facilitated the extinction of 30-day-old contextual fear memory, while the prior administration of SR (0.2 mg/kg, i.p.) antagonized this response. The facilitative effect of WIN on memory extinction does not seem to be specific for contextual fear memory because it was also observed in the water maze reversal task. CONCLUSIONS: These results suggest cannabinoid receptor agonists as potential drugs to treat anxiety disorders related to the retrieval of aversive memories.

Animals↗
PubMed2006

Effect of paroxetine on enhanced contextual fear induced by single prolonged stress in rats.

RATIONALE: Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD) that can reproduce enhanced hypothalamo-pituitary-adrenal negative feedback. OBJECTIVES: We examined whether SPS can produce an enhanced psychophysiological reactivity to laboratory stressors unrelated to trauma and whether paroxetine (PRX) can alleviate the enhanced anxiety and fear response in rats subjected to SPS. Furthermore, the effect of PRX on pain sensitivity was examined in rats with and without SPS. METHODS: Rats were subjected to SPS (restraint for 2 h, forced swim for 20 min, and ether anesthesia) and then kept undisturbed for 14 days. After that, contextual fear response was assessed. Twenty-four hours after foot shock conditioning, freezing behavior was measured during reexposure to the shock environment for 3 min. Pain sensitivity was assessed by the flinch-jump test. PRX (0.01, 0.03, or 0.1 mg/mL) was chronically administered orally in drinking water. RESULTS: Rats subjected to SPS showed a significant increase in contextual freezing compared to rats without SPS. Chronic administration of PRX at concentrations of 0.03 and 0.1 mg/mL (which produced serum concentrations similar to those that are clinically relevant) caused significant suppression of the enhanced contextual freezing. Acute administration of PRX at a dose producing clinically relevant serum concentrations did not affect the enhanced freezing. CONCLUSIONS: Our results suggest that SPS can reproduce behavioral alteration similar to that observed in patients with PTSD, and this elevated fear response can be alleviated by the chronic administration of PRX at doses producing clinically relevant serum concentrations.

Animals↗
PubMed2007

The disruptive effects of the CB1 receptor antagonist rimonabant on extinction learning in mice are task-specific.

RATIONALE: Disruption of CB(1) receptor signaling through the use of CB(1) (-/-) mice or the CB(1) receptor antagonist rimonabant (SR141716) has been demonstrated to impair extinction of learned responses in conditioned fear and Morris water maze tasks. In contrast, CB(1) (-/-) mice exhibited normal extinction rates in an appetitively motivated operant conditioning task. OBJECTIVES: The purpose of this study was to test whether rimonabant would differentially disrupt extinction learning between fear-motivated and food-motivated tasks. MATERIALS AND METHODS: Separate groups of C57BL/6J mice were trained in two aversively motivated tasks, conditioned freezing and passive avoidance, and an appetitively motivated operant conditioning task at a fixed ratio (FR-5) schedule of food reinforcement. After acquisition, the respective reinforcers in each task were withheld, and an intraperitoneal injection of vehicle or rimonabant was given 30 min before each extinction session. RESULTS: Rimonabant (3 mg/kg) treatment significantly disrupted extinction in both the conditioned freezing and passive avoidance tasks but failed to affect extinction rates in the operant conditioning task, whether using daily or weekly extinction sessions. Interestingly, rimonabant (3 mg/kg) prevented the significant increases in lever pressing (i.e., extinction burst) that occurred during the first extinction session of the operant conditioning task. CONCLUSIONS: These results support the hypothesis that the CB(1) receptor plays a vital role in the extinction of aversive memories but is not essential for extinction of learned responses in appetitively motivated tasks.

Animals↗
PubMed2007

5-HT2 receptor mechanisms of the dorsal periaqueductal gray in the conditioned and unconditioned fear in rats.

RATIONALE: It is well known that 5-HT(2) mechanisms modulate the defensive behavior produced by the stimulation of the dorsal periaqueductal gray (dPAG). However, in spite of the notion that past stressful experiences play a role in certain types of anxiety, only studies with the stimulation of the dPAG of rats without previous aversive experience have been conducted so far. OBJECTIVES: We investigated the mediation of 5-HT(2) receptors of the dPAG in rats previously submitted to contextual fear conditioning (CFC). Defensive behaviors induced by the activation of the dPAG were assessed by measuring the lowest intensity of electric current applied to this structure (threshold) able to produce freezing and escape responses during the testing sessions of CFC in which animals were placed in a context previously paired to footshocks. The 5-HT(2) function of the dPAG in this condition was evaluated by local injections of alpha-methyl-5-HT (20 nmol/0.2 mul) and ketanserin (5 and 10 nmol/0.2 mul), selective agonist and antagonist of 5-HT(2) receptors, respectively. RESULTS: In accordance with previous studies, alpha-methyl-5-HT increased the aversive thresholds (antiaversive effects) in naive rats, and injection of ketanserin into the dPAG did not produce significant effects. On the other hand, ketanserin decreased in a dose-dependent manner the freezing threshold (proaversive effect) determined by the dPAG electrical stimulation, whereas alpha-methyl-5-HT continued to show antiaversive effects in animals under CFC. CONCLUSIONS: The present results suggest that past stressful experience can produce changes in the synaptic function of 5-HT(2) receptors within the dPAG with important impact on the expression of defensive behaviors.

Animals↗
PubMed2006

Freezing of gait in Parkinson's disease.

Freezing of Gait (FOG) is one of the most disabling and least understood symptoms in Parkinson's disease (PD), and is usually observed in the advanced stage of the disease. FOG can be experienced on turning, in narrow spaces, whilst reaching a destination, and in stressful situations. FOG is commonly observed in the "off" state, but it can also be observed in the "on" state. Dual tasking (cognitive load) aggravates FOG. Visual or auditory cues often resolve FOG. Analysis of gait revealed that the rhythm of stepping suddenly jumps into high frequency (4-5 Hz) in FOG (hastening), and that floor reaction forces are disregulated. Stride-to-stride variability is increased in FOG. Hastening phenomenon was reported not only in PD patients but also in patients with striatal lesions. The basal ganglia and its frontal projections may be one of the essential lesion sites for FOG.A recent study using single-photon emission tomography (SPECT) revealed enhanced lateral premotor cortex (PMC) activity during paradoxical gait in PD, suggesting that PMC can compensate for the impaired function of the medial frontal cortex when cued by visual input. Treatment of FOG includes behavioural, medical, and surgical approaches. Tricks of all kinds (including external cues) are effective therapeutic approaches. If FOG occurs predominantly in the "off" state, dopaminergic therapy can be increased. For "on" freezing or if "on" response is otherwise optimised, the dose of the dopaminergic agent may be manipulated, but it could lead to the deterioration of parkinsonism. Deep brain stimulation of the STN often alleviates FOG in the "off" state.

Freezing Reaction, Cataleptic↗
PubMed2006

Pharmacological profile of the "triple" monoamine neurotransmitter uptake inhibitor, DOV 102,677.

1. The molecular and behavioral pharmacology of DOV 102,677 is characterized. 2. This characterization was performed using radioligand binding and neurotransmitter uptake assays targeting the monoamine neurotransmitter receptors. In addition, the effects of DOV 102,677 on extracellular neurotransmitter levels were investigated using in vivo microdialysis. Finally, the effects of DOV 102,677 in the forced swim test, locomotor function, and response to prepulse inhibition was investigated.3. DOV 102,677 is a novel, "triple" uptake inhibitor that suppresses [(3)H]dopamine (DA), [(3)H]norepinephrine (NE) and [(3)H]serotonin (5-HT) uptake by recombinant human transporters with IC(50) values of 129, 103 and 133 nM, respectively. Radioligand binding to the dopamine (DAT), norepinephrine (NET), and serotonin (SERT) transporters is inhibited with k (i) values of 222, 1030, and 740 nM, respectively. DOV 102,677 (20 mg/kg IP) increased extracellular levels of DA and 5-HT in the prefrontal cortex to 320 and 280% above baseline 100 min after administration. DA levels were stably increased for the duration (240 min) of the study, but serotonin levels declined to baseline by 200 min after administration. NE levels increased linearly to a maximum of 348% at 240 min post-dosing. Consistent with these increases in NE levels, the density of beta-adrenoceptors was selectively decreased in the cortex of rats treated with DOV 102,677 (20 mg/kg per day, PO, 35 days). 4. DOV 102,677 dose-dependently reduced the amount of time spent immobile by rats in the forced swim test, a model predictive of antidepressant activity, with a minimum effective dose (MED) of 20 mg/kg and a maximal efficacy comparable to imipramine. This decrease in immobility time did not appear to result from increased motor activity. Further, DOV 102,677 was as effective as methylphenidate in reducing the amplitude of the startle response in juvenile mice, without notably altering motor activity. 5. In summary, DOV 102,677 is an orally active, "balanced" inhibitor of DAT, NET and SERT with therapeutic versatility in treating neuropsychiatric disorders beyond depression.

Acclimatization↗
PubMed2006

Hematological parameters in wistar rats in conditions of stress and treatment with heparin.

The effects on hematological measures of emotional tension arising during the formation of food-procuring behavior in a multiple-choice maze and in conditions of pain (injection of 0.85% physiological saline i.m., 0.3 ml, daily for five days) were studied in Wistar rats. Physiological saline and training of intact animals led to increases in RBC volume and mean corpuscular hemoglobin content, accompanied by significant increases in plasma corticosterone levels. At the same time, neither heparin (standard unfractionated heparin, Serva, doses of 64 and 640 IU/kg, daily for five days) nor training of heparinized rats produced any changes in these measures. The high levels of organization of the acquired behavior and the working capacity seen in heparinized rats were evidence for improvements in both the associative properties of conditioned reflex activity and the mechanisms supporting stable reproduction of the acquired habit. After administration of heparin, rats lost all types of manifestation reflecting psychoemotional tension as generally seen in animals in the active (administration of physiological saline) and passive (intact rats) controls.

Analysis of Variance↗
PubMed2005

Immunological stress at the maternal-foetal interface: a link between neurodevelopment and adult psychopathology.

Maternal infection during pregnancy is associated with a higher incidence of mental disorders, including schizophrenia, in the offspring in later life. Our recent attempt to study this link between prenatal immunological challenge and subsequent psychopathology has led to the establishment of a mouse model demonstrating the emergence of multiple psychotic-like phenotypes following immunological challenge on gestation day (GD) 9. However, little is known about the impact of similar in utero challenge at different times of pregnancy. Here, we compare the efficacy of identical maternal immune stimulation induced by the exposure to polyriboinosinic-polyribocytidilic acid (Poly(I:C)) at a dose of 5mg/kg (i.v.) on distinct days of gestation (GD 6, 9, 13 or 17). The offspring derived were then compared to those collected from vehicle- and non-treated dams in two paradigms of selective associative learning: latent inhibition (LI) and the US-pre-exposure effect (USPEE). LI deficiency was observed in animals born to dams treated with Poly(I:C) on GD 6, 9 or 13, but not in those on GD17. In contrast, a loss of the USPEE was equivalently seen in all Poly(I:C) treatment groups, regardless of treatment times. Evaluation of the acute cytokine response in a separate cohort of pregnant dams receiving Poly(I:C) challenge on either GD9 or GD17 revealed that the ratio of interleukin-10/tumor necrosis factor-alpha was elevated in the GD17 relative to the GD9 group. The present report thus provides evidence that the acute cytokine reaction as well as the long-term pattern of behavioural sequelae of maternal immune challenge can be affected by its precise timing during pregnancy. The present study provides further support to the use of the prenatal Poly(I:C) model in the elucidation of mechanisms involved in the aetiology and disease process of immuno-precipitated neurodevelopmental mental diseases, including but not limited to, schizophrenia.

Analysis of Variance↗