Biomedical subjects

J Landeira-Fernandez

Publications and source records attributed to J Landeira-Fernandez.

At least 19 recordsLinked to original sources

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

Immediate shock deficit in fear conditioning: effects of shock manipulations.

Pavlovian contextual fear conditioning occurs when an aversive unconditional stimulus (US), such as a footshock, is presented to a rat shortly after it is placed in an experimental context. Contextual fear conditioning does not occur when the shock is presented immediately upon placement of the rat in the novel chamber. In the present study, the authors report that increasing either the number of immediate shock sessions (Experiment 1) or the immediate shock duration (Experiment 2) did not reverse this deficit. However, immediate shock seems to sensitize subsequent context conditioning (Experiment 3). These findings suggest that the associative deficit produced by immediate shock is not related to the rat's ability to process the footshock US.

Animals↗

PubMed2005

Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze.

RATIONALE: Although 5-HT2 receptors seem to play an important role in anxiety, results from numerous studies are still highly variable. Moreover, little is known about the behavioral effects of centrally administered 5-HT2 compounds in animal models of anxiety. OBJECTIVE: The current study was performed to: (1) further investigate the effects of 5-HT2 receptor activation in rats exposed to the elevated plus-maze (EPM) and the open-field arena, two widely used animal models for studying anxiety and locomotor activity; and (2) evaluate the involvement of the 5-HT2 receptors within the basolateral nucleus of the amygdala (BLA) in the modulation of such effects. METHODS: In the first experiment, male Wistar rats were exposed for 5 min to the EPM 27 min following intraperitoneal (i.p.) (1.0 ml/kg) injections of the preferential 5-HT2C receptor agonist 6-chloro-2[1-piperazinyl]pyrazine (MK-212) at doses of 1.0, 2.0, or 4.0 mg/kg. Control animals were injected with saline. The percentage of open-arm entries and the percentage of time spent in these arms were employed as anxiety indexes, whereas the number of closed-arm entries was calculated as indicative of locomotor activity. In the second experiment, rats were exposed for 10 min in an open-field arena to further assess the interference of the same MK-212 doses upon locomotor activity. In Experiment 3, rats were microinjected (0.2 microl) either with the mixed 5-HT 2A/2C receptor antagonist ritanserin (0.5, 1.25, 2.5, and 5.0 microg) or its vehicle into the BLA 12 min following i.p. injections of saline or the intermediate dose of MK-212 (2.0 mg/kg). Fifteen minutes later, each animal was exposed to the EPM as before. RESULTS: Whereas the highest dose of MK-212 (4.0 mg/kg) induced motor-suppressant effects in both EPM and open-field arena, the intermediate dose of the drug (2.0 mg/kg) reduced open-arm exploration without significantly affecting the number of closed-arm entries. This behavioral profile, consistent with selective anxiogenic effect in the EPM, was dose-dependently prevented by ritanserin microinfusion into the BLA. In saline-pretreated animals, however, ritanserin (all doses) was ineffective. CONCLUSIONS: MK-212 increases anxiety and decreases locomotor activity. The anxiogenic-like profile of 5-HT2 receptor activation is prevented by the blockade of 5-HT2 receptors within the BLA, which does not have an effect by itself upon basal anxiety levels triggered by the EPM.

Amygdala↗

PubMed2004

Analysis of the cold-water restraint procedure in gastric ulceration and body temperature.

Gastric mucosal injury induced by body restraint can be enhanced when combined with cold-water immersion. Based on this fact, the present study had two main purposes: (i) to examine the contribution of each of these two forms of stress on the development of gastric ulceration and regulation of body temperature and (ii) to investigate the importance of the animal's consciousness on gastric ulceration induced by the cold-water restraint. Independent groups of animals were exposed for 3 h to one of the following stressful treatments: body restraint plus cold-water (20+1 degrees C) immersion, body restraint alone or cold-water immersion alone. Control animals were not exposed to any form of stress. Half of the animals submitted to each of the four treatments were anesthetized with thionembutal (35 mg/kg), whereas the other half was injected with saline. Results indicated that body restraint alone was not sufficient to induce gastric ulceration or changes in body temperature. On the other hand, cold-water exposure, either alone or in conjunction with body restraint, induced the same amount of stomach erosions and hypothermia. Therefore, it appears that body restraint does not play an important role on gastric ulceration induced by the cold-water restraint procedure. Present results also indicated that conscious and anesthetized animals immersed in cold water presented robust gastric ulceration and a marked drop in body temperature. However, conscious animals developed more severe gastric damage in comparison to anesthetized animals although both groups presented the same degree of hypothermia. These findings suggest that hypothermia resulting from cold-water exposure has a deleterious effect on gastric ulceration but the animal's conscious activity during the cold-water immersion increases the severity of gastric mucosal damage. It is concluded that cold-water restraint is a useful procedure for the study of the underlying mechanisms involved in stress-induced ulceration.

Analysis of Variance↗

PubMed2004

Anxiogenic effects in the rat elevated plus-maze of 5-HT(2C) agonists into ventral but not dorsal hippocampus.

The effect of the non-selective 5-HT2C receptor agonist trifluoromethyl-phenylpiperazine (TFMPP, 0.75, 1.5 and 3.0 microg) and the preferential 5-HT2C agonist 6-chloro-2(1-piperazinyl)pyrazine (MK-212, 0.1, 0.3 and 1.0 microg) microinjected into the ventral or dorsal hippocampus was investigated in anxiety measures of rats exposed to the elevated plus-maze test. Ventral hippocampal (VH) microinjections of the 0.75 or 1.5 microg doses of TFMPP reduced open-arm exploration without affecting the number of closed-arm entries, indicating a selective anxiogenic profile. The highest dose (3.0 microg) reduced open- and closed-arm entries, suggesting interference in locomotor activity. The 0.1 microg dose of MK-212 also caused a selective anxiogenic effect when microinjected into the ventral hippocampus, without disturbing locomotor activity. Microinjections of the two higher doses of MK-212 (0.3 or 1.0 microg) into the ventral hippocampus led to a decrease of exploration in both arms of the maze. In contrast to the anxiogenic effect observed in the VH, neither TFMPP nor MK-212 significantly changed anxiety measures when microinjected into the dorsal hippocampus. These results suggest that activation of 5-HT2C postsynaptic receptors located in the ventral, but not in the dorsal, hippocampus play an important role in anxiety triggered by the elevated plus-maze test.

Animals↗

PubMed2003

Context fear conditioning inhibits panic-like behavior elicited by electrical stimulation of dorsal periaqueductal gray.

Context fear conditioning has been widely used as an animal model of anxiety whereas electrical stimulation of the dorsal portion of the periaqueductal gray (DPAG) as a model of panic attack. The present study employed these two animal models in order to investigate the influence of anxiety in the occurrence of panic attack. Results indicated that animals exposed to contextual cues that were previously associated with electrical footshocks engaged in robust defensive freezing behavior and were less likely to display flight evoked by electrical stimulation of the DPAG when compared with control animals that were not exposed to the context fear conditioning procedure. These results indicate that activation of the brain mechanisms that underlie anxiety produces an inhibitory effect on panic attack.

Animals↗

PubMed2003

Antinociception induced by stimulation of ventrolateral periaqueductal gray at the freezing threshold is regulated by opioid and 5-HT2A receptors as assessed by the tail-flick and formalin tests.

It has been suggested that antinociception is part of the animal's defensive reaction to threatening situations. Chemical or electrical stimulation of the ventrolateral portion of the periaqueductal gray (vlPAG) produces both defensive freezing behavior and antinociception, supporting the view that the vlPAG is a critical structure in the coordination of the defensive reaction. The present study indicated that electrical stimulation of the vlPAG, at a current intensity sufficient to induce defensive freezing, caused a decrease in reactivity to a phasic escapable noxious stimulus (as measured in the tail-flick test) and to a tonic, inescapable noxious stimulus (as measured in the formalin test). These antinociceptive effects were reversed by microinjections of the opioid antagonist naltrexone or the specific 5-HT2A receptor antagonist ketanserin into the stimulation sites. These results suggest that (a) activation of neural circuits of the vlPAG, responsible for the production of freezing behavior, reduces the reactivity to nociceptive stimuli (as evaluated by the tail-flick and formalin tests) and that (b) opioid- and 5-HT2A-mediated mechanisms are called into action for regulating the antinociceptive response that accompanies the freezing behavior induced by vlPAG stimulation.

Algorithms↗

PubMed2002

Distinct contributions of median raphe nucleus to contextual fear conditioning and fear-potentiated startle.

Ascending 5-HT projections from the median raphe nucleus (MRN), probably to the hippocampus, are implicated in the acquisition of contextual fear (background stimuli), as assessed by freezing behavior. Foreground cues like light, used as a conditioned stimulus (CS) in classical fear conditioning, also cause freezing through thalamic transmission to the amygdala. As the MRN projects to the hippocampus and amygdala, the role of this raphe nucleus in fear conditioning to explicit cues remains to be explained. Here we analyzed the behavior of rats with MRN electrolytic lesions in a contextual conditioning situation and in a fear-potentiated startle procedure. The animals received MRN electrolytic lesions either before or on the day after two consecutive training sessions in which they were submitted to 10 conditioning trials, each in an experimental chamber (same context) where they received foot-shocks (0.6 mA, 1 sec) paired to a 4-sec light CS. Seven to ten days later, the animals were submitted to testing sessions for assessing conditioned fear when they were placed for five shocks, and the duration of contextual freezing was recorded. The animals were then submitted to a fear-potentiated startle in response to a 4-sec light-CS, followed by white noise (100 dB, 50 ms). Control rats (sham) tested in the same context showed more freezing than did rats with pre- or post-training MRN lesions. Startle was clearly potentiated in the presence of light-CS in the sham-lesioned animals. Whereas pre-training lesions reduced both freezing and fear-potentiated startle, the post-training lesions reduced only freezing to context, without changing the fear-potentiated startle. In a second experiment, neurotoxic lesions of the MRN with local injections of N-methyl-D-aspartate or the activation of 5-HT1A somatodendritic auto-receptors of the MRN by microinjections of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) before the training sessions also reduced the amount of freezing and the fear-potentiated startle. Freezing is a prominent response of contextual fear conditioning, but does not seem to be crucial for the enhancement of the startle reflex by explicit aversive cues. As fear-potentiated startle may be produced in post-training lesioned rats that are unable to freeze to fear contextual stimuli, dissociable systems seem to be recruited in each condition. Thus, contextual fear and fear-potentiated startle are conveyed by distinct 5-HT-mediated circuits of the MRN.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2001

Defensive freezing evoked by electrical stimulation of the periaqueductal gray: comparison between dorsolateral and ventrolateral regions.

Previous reports indicated that ventrolateral periaqueductal gray (vlPAG) plays a role in the expression of freezing behavior whereas dorsolateral periaqueductal gray (dlPAG) is involved on both freezing and active forms of defensive behaviors. In order to evaluate the role of each of these areas in the occurrence of defensive reactions, rats were electrically stimulated either in the dlPAG or vlPAG with different stimulus frequencies. Stepwise increases in the electrical stimulation of both dlPAG or vlPAG induced initially freezing and then a jumping response. Freezing induced by vlPAG stimulation had a tendency to disappear when the stimulation was turned off whereas freezing induced by dlPAG stimulation remained high in the absence of the stimulation. These results suggest that dlPAG and vlPAG are involved on defensive freezing probably through different neural circuitries.

Analysis of Variance↗

PubMed2001

Dorsolateral and ventral regions of the periaqueductal gray matter are involved in distinct types of fear.

Stepwise increases in the electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) produces alertness, then freezing and finally escape. This paper examines whether this freezing is (i) caused by Pavlovian fear conditioning to the contextual cues present during stimulation and (ii) the result of the stimulation of neurons located inside the dlPAG or elsewhere. To this end, freezing behavior was assessed in rats exposed either to the same or a different environment (context shift test) following the application of either footshocks or stimulation of the dlPAG at the freezing threshold. Rats submitted to footshocks presented freezing to the context 24h later whereas rats submitted to the dlPAG stimulation showed freezing only immediately after the stimulation, regardless of the context. In the second experiment, aversive states generated by activation of the dlPAG were assessed either by measuring the thresholds for freezing and escape responses or the duration of these responses following microinjections of semicarbazide inside the dlPAG. The duration of freezing behavior was also measured in rats submitted to a contextual fear-conditioning paradigm using footshocks as unconditioned stimulus. Lesions of the ventral periaqueductal gray (vPAG) disrupted conditioned freezing to contextual cues associated to footshocks but vPAG lesions did not change the threshold of either freezing or escape responses elicited by electrical stimulation of the dlPAG. Lesions of the vPAG did not change the amount of freezing or escape responses produced by microinjections of semicarbazide into the dlPAG. These results indicate that stimulation of dlPAG neurons produce freezing behavior independent of any contextual fear conditioning and add to previously reported evidence showing that the vPAG is a critical structure for the expression of conditioned fear. In contrast, the neural substrate of unconditioned dlPAG stimulation-induced freezing is likely to elaborate unconditioned fear responses to impending danger, which have been implicated in panic disorder.

Animals↗

PubMed1999

Gastric mucosal erosion produced by NMDA microinfusions in the lateral hypothalamus: effect of selective knife cuts.

Bilateral infusions of N-methyl-D-aspartate (NMDA) into the lateral hypothalamus (LH) produce gastric erosions in rats. The present study attempted to determine the neural pathways that mediate this effect. In order to interrupt axonal transmission, knife cuts (KC) were made in different planes adjacent to the LH. In separate groups of rats, KC were made anterior, posterior or lateral to the LH just prior to bilateral NMDA infusions (20 micrograms/microliter). The incidence of gastric erosions was measured 24 h after NMDA infusions. Animals receiving sham KC and infused with NMDA exhibited significantly more gastric erosions than those infused with vehicle. Lateral parasagittal KC blocked the occurrence of gastric erosions produced by NMDA, whereas anterior coronal KC significantly increased the incidence of erosions produced by NMDA. Posterior coronal KC did not alter the incidence of gastric erosions produced by NMDA infusions into the LH. These results suggest that intrinsic LH neurons with gastric function project axons laterally and probably descend through the internal capsule to brainstem medullary nuclei. The results of the anterior KC suggest that the LH sends and/or receives inhibitory projections from neural structures (possibly the amygdaloid complex) anterior to the plane of the KC.

Animals↗

PubMed1999

Infusion of neurotoxic doses of N-methyl-D-aspartate into the lateral hypothalamus in rats produces stomach erosions, hyperthermia, and a disruption in eating behavior.

The present study examined whether damage to intrinsic lateral hypothalamic (LH) neurons induced by microinfusions of N-methyl-D-aspartate (NMDA) would produce effects similar to those seen after electrolytic LH lesions. In Experiment 1, rats receiving electrolytic (1.2 mA anodal current, 10 s) LH lesions displayed motor impairments, whereas those receiving NMDA (20 microg/microl) infusions did not. Both electrolytic lesions and NMDA infusions were associated with eating deficits, hyperthermia, and gastric erosion formation 24 hr after surgery. In Experiment 2, either 20 microg/microl or 10 microg/microl NMDA destroyed LH cells and produced dose-dependent gastric mucosal erosions as well as similar increases in body temperature. These results indicate that an alteration in the acute activity of intrinsic LH neurons plays a role in the production of gastric mucosal injury and hyperthermia and lend support to other studies implicating a role of LH neurons in eating behavior.

Animals↗

PubMed1996

Context and Pavlovian conditioning.

Procedurally, learning has to occur in a context. Several lines of evidence suggest that contextual stimuli actively affect learning and expression of the conditional response. The experimental context can become associated with the unconditional stimulus (US), especially when the US is presented in a context in the absence of a discrete conditional stimulus (CS). Moreover, context can modulate CS-US associations. Finally, it appears that context can become associated with the CS when it is presented before the CS-US training. The purpose of the present paper is to review some of the relevant literature that considers the context as an important feature of Pavlovian conditioning and to discuss some of the main learning theories that incorporate the context into their theoretical framework. The paper starts by mentioning historical positions that considered context an important variable in conditioning and then describes how the approach to contextual conditioning changed with the modern study of Pavlovian conditioning. Various forms of measurement of context conditioning are presented and the associative strength attached to context in several experimental paradigms is examined. The possible functions that context may acquire during conditioning are pointed out and related to major learning theories. Moreover, the effect of certain neurological manipulations on context conditioning is presented and these results are discussed in terms of possible functions that the context might acquire during Pavlovian conditioning. It is concluded that contextual stimuli acquire different functions during normal conditioning. A procedure in which animals are exposed to an aversive US immediately after they are placed in the experimental context is suggested as a useful control for the study of context conditioning.

Animals↗

PubMed1992

Selective impairment of long-term but not short-term conditional fear by the N-methyl-D-aspartate antagonist APV.

Previous research has indicated that the competitive N-methyl-D-aspartate (NMDA) antagonist APV (DL-2-amino-5-phosphonovalerate) prevents the Pavlovian conditioning of fear to contextual stimuli when tested 24 hr, but not immediately, after training. The present study investigated this differential time-dependent effect of APV on fear conditioning. Rats were given either APV or saline and presented with 3 footshocks in a distinctive chamber. Promptly after the shock, rats that had received APV exhibited a species-typical fear response-freezing. However, the freezing lasted for only a short period of time (less than 3 min) compared with that of controls. An immediate-shock procedure showed that freezing was entirely a conditional response to the chamber. In addition, the results of a savings test suggest that APV impairs storage rather than retrieval processes. These results indicate that there are two temporally distinct associative fear processes, a short-term NMDA-independent conditional fear and a long-term NMDA-dependent conditional fear.

2-Amino-5-phosphonovalerate↗

PubMed1992

Unit activity to click CS changes in dorsal cochlear nucleus after conditioning.

Recordings were made of single unit activity (n = 360 units) from the dorsal cochlear nucleus of cats. Different patterns of activity were elicited by acoustic stimuli before and after Pavlovian conditioning. The peak response to a forward paired click conditioned stimulus (CS) increased whereas that to a backward paired hiss discriminative stimulus (DS) did not. The percentage of units responding to the CS increased from 34% to 46% after conditioning. The findings do not support the widely accepted hypothesis that learning has no effect on transmission through the first brain stem relay of the auditory system and indicate, instead, that the cochlear nucleus can participate in complex adaptive acoustic signal processing.

Acoustic Stimulation↗

PubMed1991

N-methyl-D-aspartate receptor antagonist APV blocks acquisition but not expression of fear conditioning.

The role of N-methyl-D-aspartate (NMDA) receptors in Pavlovian fear conditioning was examined using the NMDA antagonist DL-2-amino-5-phosphonovaleric acid (APV). Either APV (5 micrograms/rat) or saline was administered before the training phase, the testing phase, or both. APV completely blocked acquisition but not expression of fear conditioning. The L enantiomer of APV did not affect the acquisition of conditional fear. To separate encoding from consolidation processes, APV was administered either before or immediately after the footshock unconditional stimulus (US) during the training phase. The results indicate that APV must be present during the US to produce its effects on fear conditioning. The behavioral effect of the drug is not due to analgesic action because APV did not alter pain sensitivity. The data suggest that NMDA receptors are critical for the acquisition but not expression of fear conditioning. These effects on fear conditioning are parallel to the in vitro effects of APV on the acquisition but not expression of long-term potentiation (LTP) and suggest that endogenously generated NMDA-dependent LTP participates in the neural plasticity underlying fear conditioning.

2-Amino-5-phosphonovalerate↗

PubMed1991

The dentate nucleus is a short-latency relay of a primary auditory transmission pathway.

Recordings of unit activity showing 4-6 ms latency responses to a click stimulus provided evidence that the dentate nucleus could function as a short-latency auditory relay. On the basis of these findings, plus fiber fillings from injections of phaseolus leucoagglutinin into the dentate, a new auditory pathway between dorsal and ventral cochlear nuclei, dentate nucleus, and rostral thalamus is proposed. The pathway could provide direct, short-latency transmissions to the motor cortex that bypass the classical auditory receptive cortex.

Acoustic Stimulation↗

PubMed1990

Conditional hypoalgesia is attenuated by naltrexone applied to the periaqueductal gray.

The ventrolateral periaqueductal gray (vPAG) is an important component in a brainstem system involved in the endogenous modulation of nociception and defensive behavior. The present study was conducted to determine if opioid receptors within the vPAG contribute to the hypoalgesia seen in rats during presentation of a Pavlovian CS for footshock. Independent groups of animals received microinjections of either 5.0 micrograms naltrexone HCl or vehicle into the vPAG prior to being placed in an observation chamber in which shock had been delivered 24 h earlier. Nociceptive reactivity was measured with the formalin test. Naltrexone treatment attenuated conditional hypoalgesia but did not affect formalin-induced behavior in non-shocked rats. Naltrexone had no effect on the amount of defensive freezing behavior observed during the test session. These results indicate that conditional hypoalgesia as measured by the formalin test involves the activation of documented brainstem antinociceptive systems.

Animals↗