Biomedical subjects

J Feldon

Publications and source records attributed to J Feldon.

At least 55 records · Page 3Linked to original sources

PubMed2001

Latent inhibition, but not prepulse inhibition, is reduced during withdrawal from an escalating dosage schedule of amphetamine.

The enhanced locomotor and stereotypic responses of the rat to repeated amphetamine (AMPH) administration are considered to be an animal model of positive schizophrenic symptoms. In contrast, behaviors observed during withdrawal from repeated AMPH are believed to model depression or anxiety. In the present study, the authors tested whether AMPH withdrawal might also elicit behaviors consistent with animal models of schizophrenia, specifically, disruptions in latent inhibition (LI) of 2-way active avoidance and prepulse inhibition (PPI) of startle. Rats treated with escalating doses of AMPH (6 days, 1-5 mg/kg ip) or saline were tested for LI and PPI during withdrawal. LI was eliminated by prior AMPH treatment in rats tested at 4, 13, and 28 days of withdrawal. In contrast, PPI did not differ between AMPH and control groups. These results support an interrelationship between repeated-AMPH and LI-disruption, but not PPI-disruption, models of schizophrenia.

Amphetamine↗

PubMed2001

Comparison of the effects of infant handling, isolation, and nonhandling on acoustic startle, prepulse inhibition, locomotion, and HPA activity in the adult rat.

This study examined whether early isolation (EI), early handling (EH), or early nonhandling (NH) in infant rats alters (a) prepulse inhibition (PPI) of the acoustic startle response (ASR) or its disruption by apomorphine, (b) motor activity or its stimulation by amphetamine, or (c) corticosterone activity (because of its modulation of dopamine activity), in adulthood and in comparison with a normal-husbandry postnatal control environment. EI did not affect PPI, reduced PPI disruption by apomorphine in males, and increased amphetamine-stimulated activity in males. NH increased the ASR, reduced activity in the open field, and increased corticosterone reactivity in males. In all paradigms, the effects of EH were similar to those of the control environment. This study provides an important contribution to the evidence on the relationship between postnatal experience and long-term neurobehavioral development in the rat and the relevance of this approach to animal models of neuropsychiatric disorder.

Age Factors↗

PubMed2001

Acute withdrawal from repeated cocaine treatment enhances latent inhibition of a conditioned fear response.

Psychostimulant-induced locomotor sensitization and disrupted latent inhibition (LI) of a classically conditioned association are two paradigms that have been widely studied as animal behavioural models of psychosis. In this study we assessed the effects of withdrawal from the repeated intermittent administration of cocaine on LI of a conditioned fear response. Animals which were either preexposed (PE) to a tone conditioned stimulus (CS) or naive to the tone (i.e. non-preexposed: NPE) subsequently experienced 10 pairings of the tone CS with footshock. Afterwards, both groups received five daily injections of cocaine (20 mg/kg, i.p.) or saline. After 3 days of withdrawal from drug treatment, animals were tested for conditioned freezing to the context of the footshock chamber, and 1 day later, for conditioned freezing to the tone CS. Cocaine-sensitized animals exhibited markedly enhanced LI compared to saline-treated animals, due to the fact that NPE-cocaine animals spent more time freezing during the tone CS than NPE-saline animals, whereas PE-cocaine animals showed a tendency toward reduced freezing compared to the saline groups. While these results suggest the presence of increased anxiety in cocaine-withdrawn NPE animals, the absence of this effect in cocaine-withdrawn PE rats indicates that cocaine withdrawal also influences the retrieval of previously learned information.

Acoustic Stimulation↗

PubMed2000

Activation of the retrohippocampal region in the rat causes dopamine release in the nucleus accumbens: disruption by fornix section.

There is a well-described projection from the retrohippocampus (subiculum and entorhinal cortex) to the nucleus accumbens that is involved in the control of psychomotor behaviour, and is implicated in the aetiology of schizophrenia. Cortical abnormalities are widely reported in the brains of schizophrenic patients, but it is unclear whether they are the cause or consequence of those changes in subcortical systems that are treated with neuroleptic drugs. We have, therefore, conducted a series of microdialysis experiments in anaesthetized rats to determine whether infusion of the excitotoxin, N-methyl-D-aspartate, into the retrohippocampus increases mesolimbic dopamine release. We found a clear and reproducible increase in extracellular dopamine in the nucleus accumbens following N-methyl-D-aspartate (2.5 microg), that was abolished when we sectioned the fimbria-fornix. Furthermore, inhibition of gamma-aminobutyric acid receptors following retrohippocampus administration of bicuculline (4 microg), also increased dopamine in the nucleus accumbens. The dopamine response to bicuculline was accompanied by an increase in dopamine metabolism, was long lasting, and also reduced by fornix section.The response to both N-methyl-D-aspartate and bicuculline depends on the integrity of the projection from the retrohippocampus to the nucleus accumbens. The results provide an underlying mechanism whereby a primary insult in the temporal cortex, caused by excessive N-methyl-D-aspartate receptor stimulation, can produce a hyperdopaminergic state. In addition, an increase in subiculo-accumbens activity evoked by bicuculline may also explain why patients with limbic epilepsy can develop a psychosis.

Animals↗

PubMed2000

Effect of amphetamine on extracellular acetylcholine and monoamine levels in subterritories of the rat medial prefrontal cortex.

The present study sought to investigate the contributions of the dorsal prelimbic/anterior cingulate and ventral prelimbic/infralimbic cortices to the reverse microdialysis of amphetamine (1, 10, 100, 500, and 1000 microM) on dialysate acetylcholine, choline, norepinephrine, and serotonin levels. The results demonstrate that basal levels of acetylcholine, choline, and serotonin were homogeneous within subregions of the medial prefrontal cortex. In contrast, dialysate norepinephrine levels were significantly higher in the anterior cingulate cortex compared with the infralimbic cortex. Reverse microdialysis of amphetamine in both subareas of the medial prefrontal cortex produced a dose-dependent increase in norepinephrine and serotonin levels; the magnitude of this effect was similar in both subterritories of the medial prefrontal cortex. Microinfusion of amphetamine increased dialysate acetylcholine levels in a dose-dependent manner only in the infralimbic cortex. Finally, amphetamine decreased choline levels in both subregions of the medial prefrontal cortex. The magnitude of this effect was larger in the anterior cingulate cortex compared with its infralimbic counterpart. Since depletions of frontal cortical acetylcholine result in severe cognitive deficits, the present data raise the possibility that the type of neural integrative processes that acetylcholine mediates depends, at least in part, on the subterritories that characterize the medial prefrontal cortex.

Acetylcholine↗

PubMed2000

Lack of effect of an early stressful life event on sensorimotor gating in adult rats.

Hypotheses of the etiology of schizophrenia emphasize the important role of perinatal insults in predisposing individuals to the development of the disease, so that an animal model in which a discrete postnatal manipulation of the infant social environment yields schizophrenia-like behavior in adulthood would be valuable in terms of the study of the neural substrate and treatment of schizophrenia. Schizophrenics demonstrate a deficit in sensorimotor gating (prepulse inhibition), and a similar phenomenon has been described in adult rats following the administration of direct and indirect dopamine agonists. Recently it has been reported that a 24 h separation of rat pups from the mother results in a disruption of prepulse inhibition at adulthood. Here we report a study which investigated the same phenomenon but which, in contrast to the previous study, utilized unrelated subjects all derived from different dams. Maternal separation was conducted for 24 h with pups aged 4, 9 or 18 days and these subjects, together with non-separated controls, were tested at age 3 months in terms of their prepulse inhibition in the acoustic startle response paradigm. Maternal separation did not disrupt prepulse inhibition. Comparison of males and females (with a maximum of one opposite-sex sibling) demonstrated that acoustic startle response and prepulse inhibition of this response was enhanced in males relative to females. This study indicates that 24 h maternal separation does not provide a robust model for studying the effects of early environmental insults on the long-term abnormal development of sensorimotor gating.

Acoustic Stimulation↗

PubMed2000

The expression of the calcium binding protein calretinin in the rat striatum: effects of dopamine depletion and L-DOPA treatment.

The activity of the striatum is regulated by glutamate and dopamine neurotransmission. Consequent to striatal dopamine depletion the corticostriatal excitatory input is increased, which in turn can raise intracellular calcium levels. We investigated changes in the neuronal expression of the calcium binding protein calretinin related to dopamine depletion and l-DOPA administration. Immunohistochemical methods were used to assess calretinin in the striatum of rats with unilateral lesions of the nigrostriatal system. In these animals we observed a loss of the patchy distribution of calretinin fibers. Moreover, after dopaminergic depletion we detected two new, not previously described, calretinin cell types, the presence of which could be related to morphological changes induced by loss of a dopaminergic input. We also found an increase in the number of calretinin-labeled cells in the striatum ipsilateral to the lesion compared to the contralateral striatum or to the striatum of normal rats. This increase was mostly evident at 3 weeks postlesion and tended to decrease toward normal levels at 6, 10, and 18 weeks postlesion. In unlesioned animals, l-DOPA administration did not induce changes in the expression of calretinin. In unilaterally lesioned animals, l-DOPA reversed the increase in the number of calretinin-positive cells induced by the lesion. However, chronic l-DOPA administration was less effective than acute l-DOPA in reversing the effect of the lesion. The present data suggests that striatal calretinin neurons are sensitive to dopamine depletion. Increased expression of calretinin in striatal cells may be consequent to enhanced striatal excitatory input.

Animals↗

PubMed2000

Blockade of latent inhibition following pharmacological increase or decrease of GABA(A) transmission.

The latent inhibition (LI) phenomenon refers to the retardation in learning of an association between a stimulus and a consequence if that stimulus had been previously experienced without consequence. An earlier study demonstrated that the benzodiazepine receptor agonist chlordiazepoxide (CDP), when administered before the phase of preexposure to the to-be-conditioned stimulus, impaired animals' ability to develop LI. The present study was designed to investigate the effect of the anxiogenic drugs pentylenetetrazole (PTZ) and the benzodiazepine partial inverse agonist Ro15-4513 on LI. Both anxiogenics, in contrast to CDP, are known for their GABA inhibitory action. The effects produced by the combined administration of a GABAergic function facilitator and inhibitor (CDP/PTZ and CDP/Ro15-4513) were also investigated. Both anxiogenic drugs led to an attenuation of LI, and, similarly to CDP, this attenuation was exclusively due to their administration prior to the preexposure stage of the experiment. However, this effect was abolished when anxiolytic and anxiogenic drugs were administered together, suggesting a pharmacological rather than behavioral summation of effects. These data also demonstrate the bidirectional GABAergic modulation of the LI phenomenon: both increased and decreased GABA(A) receptor activation led to reduced LI, thereby suggesting that an optimal receptor activation level is necessary for the normal establishment of LI.

Affinity Labels↗

PubMed2000

Effects of MK801 and neuroleptics on prepulse inhibition: re-examination in two strains of rats.

Disruption of prepulse inhibition (PPI) induced by NMDA receptor antagonists, such as MK801, has been used as an animal model of positive and negative symptoms of schizophrenia. Previous studies suggested that atypical, but not typical, neuroleptics can selectively restore MK801-induced PPI disruption and that such selectivity may depend on strain differences. The present study re-examined PPI disruption by systemic MK801 in Wistar (WS) and Sprague-Dawley (SD) strains, and addressed the issue whether clozapine (atypical), compared to haloperidol (typical), effectively antagonizes MK801-induced PPI disruption. In addition, we tested the effects of bilateral microinfusion of MK801 into the ventral hippocampus in WS. Systemic MK801 disrupted PPI in both strains. Neither clozapine nor haloperidol antagonized MK801-induced PPI in either strain. Our clozapine data do not agree with previous reports of clozapine's ability to antagonize MK801-induced PPI disruption. Similar to previous results with SD, MK801 infusion into the ventral hippocampus failed to affect PPI in WS. In our view, the selective ability of atypical neuroleptics to restore PPI disruption by NMDA antagonists, and to serve as a tool for identifying possible atypical neuroleptics, requires further examination. PPI disruption with systemic MK801 may be due to the blockade of NMDA receptors in multiple brain sites.

Animals↗

PubMed2000

Lewis/Fischer rat strain differences in endocrine and behavioural responses to environmental challenge.

The Lewis (LEW) and Fischer (F344) rat strains provide a comparative model of hypothalamic-pituitary-adrenal (HPA) function in which LEW is relatively hypoactive at homeostasis and hyporeactive to environmental challenge. The present study describes a comparison of LEW and F344 rats, males and females, in terms of their corticosterone (CORT) or behavioural responses to a range of behavioural tasks, where each of the tasks used contains a stressor component and has been demonstrated to be sensitive to corticotropin releasing factor (CRF) and/or CORT manipulation: acoustic startle response (ASR), elevated plus maze, schedule-induced polydipsia, and fear-conditioned suppression of drinking. Our aim was to determine to what extent the LEW trait of HPA axis hyporesponsiveness is associated with strain differences in behavioural responsiveness to environmental challenge. As expected, young (2-3 months)-mature (5-10 months) LEW males and females exhibited a lesser CORT response to restraint and novel confinement than did F344 males and females, although in old adulthood (18 months) the CORT stress response was equable in LEW/F344 males and actually higher in LEW than in F344 females. In young-mature adults, the ASR was greater in LEW males than in the other groups; all groups spent a low proportion of time on the open arms of the elevated plus maze; polydipsia was greater in F344 females than in the other groups; and fear-conditioned suppression of drinking was greater in F344 males and females than in LEW males and females. Therefore, relative hyporeactivity of the HPA axis in LEW rats is clearly not associated with uniform behavioural hyporeactivity, including CRF-dependent behaviours. Rather, this study suggests further evidence that environmental reactivity reflects a number of distinct emotional states and underlying neural circuits.

Age Factors↗

PubMed2000

Effects of local infusions of dopaminergic drugs into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition and amphetamine induced activity.

Impaired ability to 'gate out' sensory and cognitive information is considered to be a central feature of schizophrenia and is manifested, among others, in disrupted prepulse inhibition (PPI) and latent inhibition (LI). The present study investigated in rats the effects of increasing or decreasing dopamine (DA) receptor activation within the medial prefrontal cortex (mPFC) by local administration of the indirect DA receptor agonist amphetamine (AMPH; 10.0 microg/side) or the DA antagonist cis-flupenthixol (FLU; 12.0 microg/side) on PPI and LI as well as on systemic AMPH-induced activity. The effects of intra-mPFC apomorphine (APO; 10.0 microg/side) on PPI were also tested. AMPH infusions decreased systemic AMPH-induced increase in locomotor activity in the open field, whereas FLU infusion was ineffective. Both infusions had no effect on LI and PPI. However, APO infusions induced a disruption of PPI. These results provide additional evidence that the mPFC is a component of the neural circuitry mediating PPI but plays no role in LI. In addition, they show that the behavioral outcomes produced by DA receptor activation/blockade in the mPFC of the rat cannot be explained by postulating a simple reciprocal relationship between the cortical and subcortical DA systems.

Amphetamine↗

PubMed2000

Long-term effects of prenatal stress experiences and postnatal maternal separation on emotionality and attentional processes.

Postnatal environmental manipulations naturally occur on the background of prenatal experiences. In the laboratory rat, both pre- and postnatal environmental manipulations have been shown to alter adult behaviour. Additionally, it has been demonstrated that the consequences of postnatal manipulations can be altered by previous prenatal stress experience (PS). In the present study, we investigated long-term behavioural consequences of combined PS and postnatal experience, namely repeated maternal separation (MS). PS primarily increases emotionality and fear-related behaviour, while postnatal repeated MS has been previously reported to affect primarily attentional processes. Thus, we tested adult male and female Wistar rats on paradigms involving both emotionality and attention, namely open field, prepulse inhibition (PPI), and latent inhibition (LI) in the active avoidance and the conditioned emotional response paradigms. In line with previous reports, PS decreased open-field locomotion and impaired avoidance learning (increased emotionality), while MS enhanced LI (selective attention) and improved avoidance learning. Further, PS also increased PPI. There was little interaction between the two manipulations: The increased PPI seen after PS was normalised by MS, and the MS-induced enhancement of LI (using the active avoidance paradigm) was not evident in subjects previously subjected to PS. Taken together, these results suggest that the effects of PS and repeated MS are not synergistic in any of the investigated paradigms but can antagonise each other. Thus, in assessing the effects of postnatal manipulations, attention should be paid to the inadvertent occurrence of prenatal stress.

Animals↗

PubMed2000

The effects of ibotenic acid lesions of the medial and lateral prefrontal cortex on latent inhibition, prepulse inhibition and amphetamine-induced hyperlocomotion.

Hypofunction of prefrontal cortical regions, such as dorsolateral and orbital regions, has been suggested to contribute to the symptomatology of schizophrenia. In the rat, the medial and the lateral prefrontal cortices are considered as homologs of the primate dorsolateral and orbital prefrontal cortices, respectively. The present study investigated in rats the effects of lesions of the medial and lateral prefrontal cortices on latent inhibition, prepulse inhibition and amphetamine-induced activity. These paradigms are known to be modulated by the mesolimbic dopaminergic system, a system that has been suggested to be involved in the symptomatology of schizophrenia. Latent inhibition and prepulse inhibition are disrupted in schizophrenic patients as well as in rats treated with amphetamine. Amphetamine-induced activity was tested under dim light (low stress) and bright light (high stress) because stressful situations selectively increase mesocortical dopamine activity. Lateral prefrontal cortex lesioned animals did not differ in their behavior from control animals in any of the paradigms used in this study. Medial prefrontal cortex lesions did not affect latent inhibition but increased prepulse inhibition. In the amphetamine-induced activity experiment, prior to drug administration, open field locomotion was reduced under bright illumination for all lesion groups. After amphetamine administration, medial prefrontal cortex lesions attenuated the hyperlocomotor effect of the drug under the dim light condition and potentiated it under the bright light condition. The results indicate that medial and lateral prefrontal cortex can be functionally differentiated by their involvement in the modulation of behavior requiring mesocorticolimbic dopamine activation. The results in amphetamine induced activity suggest that the behavioral outcomes associated with medial prefrontal cortex depend on the background (stress) against which the evaluation is made. The results also support the notion that prepulse inhibition may be a better model than latent inhibition of the symptoms of schizophrenia associated with dysfunctional prefrontal activity.

Amphetamine↗

PubMed2000

Differential involvement of dopamine in the shell and core of the nucleus accumbens in the expression of latent inhibition to an aversively conditioned stimulus.

Latent inhibition, the process whereby pre-exposure to a conditioned stimulus without consequence impairs subsequent learning of an association between the conditioned stimulus and an unconditioned stimulus, is reportedly disrupted in both amphetamine-treated rats and in acute schizophrenics. This has led to the suggestion that disruptions in latent inhibition model some of the cognitive impairments associated with hyperactive dopamine transmission as it is expressed in schizophrenic patients. Specifically, fluctuations in dopamine neurotransmission within the nucleus accumbens have been implicated in the mediation of latent inhibition; however, it has not been established whether these dopamine-mediated effects occur in the shell or core subregion of the nucleus. In the present study, 48h after conditioned stimulus-pre-exposed and non-pre-exposed animals experienced 10 pairings of tone and footshock, we measured extracellular levels of dopamine in the shell and core during the expression of latent inhibition to an aversively conditioned tone using in vivo microdialysis. Our results show that pre-exposure to the tone eliminated the conditioned release of dopamine in the shell of the nucleus accumbens and resulted in an attenuated conditioned freezing response to the tone conditioned stimulus. In contrast, dopamine release in the core was not affected by pre-exposure to the tone. These data suggest that it is specifically the shell of the nucleus accumbens in which alterations of dopaminergic tone, whether pharmacologically induced in rodents or the result of disease in humans, may act to disrupt latent inhibition.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome.

Rearing rats in isolation has been shown to be a relevant paradigm for studying early life stress and understanding the genesis of depression and related affective disorders. Recent studies from our laboratory point to the relevance of studying the social isolation syndrome as a function of home caging conditions. Accordingly, the present series of experiments assessed the contribution of each condition to the expression of the prepulse inhibition of the acoustic startle, food hoarding and spontaneous locomotor activity. In addition, ex vivo neurochemical changes in the brains of isolated and grouped rats reared either in sawdust-lined or in grid-floor cages were determined by measuring dopamine and serotonin as well as their major metabolites in a "psychosis circuit" that includes mainly the hippocampus and selected hippocampal efferent pathways projecting towards the anterior cingulate and infralimbic cortices, nucleus accumbens, dorsolateral caudate nucleus, amygdala and entorhinal cortex. The results of the present study demonstrate that rearing rats in isolation (i) produces a syndrome of generalized locomotor hyperactivity; (ii) increases the startle response; (iii) impairs prepulse inhibition; (iv) tends to increase food hoarding behavior; (v) increases basal dopamine turnover in the amygdaloid complex; (vi) decreases basal dopamine turnover in the infralimbic part of the medial prefrontal cortex; and (vii) decreases basal turnover of serotonin in the nucleus accumbens. In the entorhinal cortex, dopamine neurotransmission seemed to be more sensitive to the caging conditions since a decreased basal turnover of dopamine was observed in grid-reared animals. Plasma corticosterone levels were also increased in grid-reared animals compared with rats reared in sawdust cages. Finally, isolates reared on grids showed a significant positive correlation between plasma corticosterone levels and dopamine in the left nucleus accumbens.Altogether, these results support the contention that there is a link between social isolation, attention deficit, spontaneous locomotor hyperactivity and reduced dopamine turnover in the medial prefrontal cortex. Furthermore, our data demonstrate that rearing rats in grid-floor cages represents a form of chronic mild stress associated with increased corticosterone levels, decreased basal turnover of entorhinal dopamine and increased dopamine activity in the left nucleus accumbens. Finally, a significant and selective decrease in the basal turnover of serotonin in the nucleus accumbens of isolated rats may be linked to the isolation-induced locomotor hyperactivity.

Acoustic Stimulation↗

PubMed2000

Microinfusion of the non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) into the dorsal hippocampus of wistar rats does not affect latent inhibition and prepulse inhibition, but increases startle reaction and locomotor activity.

Latent inhibition (the retarded conditioning to a stimulus following its repeated non-reinforced pre-exposure) and prepulse inhibition (the reduction in the startle response to an intense acoustic stimulus when this stimulus is immediately preceded by a prepulse) reflect cognitive and sensorimotor gating processes, respectively, and are deficient in schizophrenic patients. The disruption of latent inhibition and prepulse inhibition in the rat is used as an animal model for the attentional deficits associated with schizophrenia. The present study tested the extent to which latent inhibition and prepulse inhibition, startle reaction and locomotor activity in the open field were affected by infusing the non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) into the dorsal hippocampus of Wistar rats. We used the same dose of MK-801 (6.25microg/0.5microl per side) previously found to be effective in the disruption of prepulse inhibition when infused into the dorsal hippocampus of Sprague-Dawley rats [Bakshi V. P. and Geyer M. A. (1998) J. Neurosci. 18, 8394-8401; Bakshi V. P. and Geyer M. A. (1999) Neuroscience 92, 113-121]. Bilateral infusion of MK-801 into the dorsal hippocampus did not disrupt latent inhibition. Furthermore, in contrast to previous studies, we failed to find a significant disruption of prepulse inhibition after MK-801 infusion into the dorsal hippocampus, although MK-801 infusion was effective in increasing the startle amplitude as well as locomotor activity in an open field. From our results, we suggest that N-methyl-D-aspartate receptor-mediated processes within the dorsal hippocampus are not necessary for the normal maintenance of the attentional processes reflected by latent inhibition and prepulse inhibition.

Animals↗

PubMed2000

Effects of administering cocaine at the same versus varying times of day on circadian activity patterns and sensitization in rats.

The effects of different schedules of cocaine administration on circadian activity patterns and locomotor sensitization were studied. Rats received intraperitoneal injections of either saline or 20 mg/kg cocaine at either 24- or 33-hr intervals for 8 cycles (development). After a 2-day withdrawal, they were given a cocaine challenge in a novel environment. Rats given cocaine at 24-hr intervals were hypoactive 4 to 9 hr postinjection during development and, during cocaine challenge, showed sensitization of locomotor activity. Rats given cocaine at 33-hr intervals did not show these effects. On the 33-hr-period schedule, activity was enhanced beginning 24 hr after drug receipt. Different intermittent schedules of cocaine receipt may alter the vulnerability to cocaine, and altered vulnerability may be more likely when a subsequent cocaine injection interacts with a distal state of sensitivity produced by a prior injection.

Animals↗

PubMed2000

Differential role of the medial and lateral prefrontal cortices in fear and anxiety.

In the rat, both the medial and lateral prefrontal cortices (PFC; mPFC and lPFC, respectively) have direct connections with limbic structures that are important in the expression of fear and anxiety. The present study investigated the behavioral effects of excitotoxic lesions of either the mPFC or the lPFC on conditioned and unconditioned fear paradigms. In both unconditioned fear paradigms (open field, elevated plus-maze), lesions of the mPFC decreased anxiety. In fear conditioning, lPFC lesions substantially increased freezing throughout the different phases of the experiment, whereas mPFC lesions increased freezing to contextual cues and showed reduced freezing to discrete cues. These results support the functional role of the PFC in mediating or modulating central states of fear and anxiety and suggest a functional dissociation between the lPFC and mPFC in their role in fear and anxiety.

Animals↗