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J Feldon

Publications and source records attributed to J Feldon.

At least 37 records · Page 2Linked to original sources
PubMed2002

Prepulse inhibition in rats with temporary inhibition/inactivation of ventral or dorsal hippocampus.

Prepulse inhibition (PPI) of the acoustic startle response is a measure of sensorimotor gating and is decreased in neuropsychiatric diseases, including schizophrenia. Hippocampal involvement in PPI has been the subject of several studies, in particular, as aberrant hippocampal activity has been associated with schizophrenia. In rats, chemical stimulation of the ventral hippocampus reduced PPI, while normal PPI was found following hippocampal lesions, suggesting that ventral hippocampal overactivity is detrimental for PPI, but that normal hippocampal activity does not contribute substantially to PPI. In the present study, we investigated the importance of hippocampal activity for PPI by examining PPI in Wistar rats with temporarily decreased hippocampal activity, aiming to avoid compensatory processes that may occur with permanent lesions. Bilateral ventral or dorsal hippocampal infusions of the gamma-aminobutyric acid A (GABA(A)) receptor agonist muscimol (1 microg/side) or the sodium-channel blocker tetrodotoxin (TTX, 10 ng/side) reduced PPI. This reduction is probably neuroleptic-resistant since haloperidol and clozapine did not antagonize the muscimol-induced decreases in PPI. PPI reduction by muscimol inhibition or TTX inactivation of the dorsal or ventral hippocampus indicates that hippocampal activity contributes to sensorimotor gating, suggesting intact PPI after permanent hippocampal lesions to reflect compensatory processes. The data are discussed with respect to hippocampal dysfunction in schizophrenia.

Animals↗
PubMed2002

A differential involvement of the shell and core subterritories of the nucleus accumbens of rats in attentional processes.

The nucleus accumbens comprises of two anatomically distinct subterritories: an inner core and an outer shell region. The distinct pattern of the core and shell input and output targets suggests that these two regions may mediate different behavioral processes. Using N-methyl-D-aspartate excitotoxic lesions in either the core or shell region, we investigated whether we can dissociate functionally these two subterritories. N-Methyl-D-aspartate-lesioned, sham-lesioned and non-operated animals were tested for locomotor activity in an open field and in two behavioral paradigms known to evaluate attentional deficits, namely the pre-pulse inhibition of the acoustic startle reflex and latent inhibition, measured in a two-way active avoidance paradigm. The shell-lesioned animals showed a small but significant hyperactivity in the open field when compared to the core-lesioned and to control animals. In the pre-pulse inhibition paradigm, core-lesioned animals demonstrated reduced pre-pulse inhibition to the two high pre-pulse intensities (80 dB[A], 84 dB[A]). In the active avoidance paradigm, whereas no lesion effects were detected in the non-pre-exposed groups, clear attenuation of latent inhibition was found in the shell-lesioned rats, in comparison to both core-lesioned and control rats, due to improved avoidance performance of the shell-pre-exposed group. From these results we suggest that the two subterritories of the nucleus accumbens are differentially involved in attention-related processes: the core lesion leads to significant disruption of pre-pulse inhibition while the shell lesion leads to heightened activity and significant attenuation of latent inhibition.

Acoustic Stimulation↗
PubMed2002

Dopamine receptor blockade in the rat medial prefrontal cortex reduces spontaneous and amphetamine-induced activity and does not affect prepulse inhibition.

The functions and interactions of cortical and subcortical dopamine systems are of interest because alterations in these systems have been implicated in neuropsychiatric diseases, such as schizophrenia. It has been proposed that prefrontal dopamine transmission may oppose dopamine transmission in subcortical sites, such as the nucleus accumbens. Accordingly, reduced prefrontal dopamine transmission would be expected to enhance or induce behavioral effects that have been associated with stimulation of accumbal dopamine receptors. In rats, spontaneous and amphetamine-induced activity is supported by dopamine receptor stimulation in the nucleus accumbens, while prepulse inhibition (PPI) of the acoustic startle response, which is used to measure sensorimotor gating and is disrupted in schizophrenia, is reduced by increased accumbal dopamine receptor stimulation. In the present experiments, we found that bilateral infusion of the dopamine D1/D2 receptor antagonist cis-flupenthixol dihydrochloride into the medial prefrontal cortex of Wistar rats (25 microg each side) reduced spontaneous activity and completely blocked induction of hyperactivity by systemic administration of D-amphetamine sulfate (1 mg/kg), while not affecting PPI. These findings do not support an antagonism between prefrontal and accumbal dopamine in the control of behavior. Rather, our data demonstrate that prefrontal dopamine transmission may modulate some behavioral processes in a similar way to accumbal dopamine.

Acoustic Stimulation↗
PubMed2001

The ventral hippocampus and fear conditioning in rats: different anterograde amnesias of fear after infusion of N-methyl-D-aspartate or its noncompetitive antagonist MK-801 into the ventral hippocampus.

Previous studies on hippocampal involvement in classical fear conditioning mainly focused on the dorsal hippocampus and conditioning to a context. However, in line with the strong interconnectivity of the ventral hippocampus with amygdala and nucleus accumbens, more recent studies indicated an even more global role for the ventral hippocampus in fear conditioning. The present study examined the formation of classical fear conditioning to explicit and contextual cues following stimulation or blockade of N-methyl-D-aspartate (NMDA) receptors in the ventral hippocampus. NMDA (0.5 microg/side) or the noncompetitive NMDA antagonist MK-801 (dizocilpine; 6.25 microg/side) were bilaterally infused into the ventral hippocampus of Wistar rats before fear conditioning to explicit and contextual cues. Conditioned fear was assessed using an automated measurement of freezing. NMDA stimulation of the ventral hippocampus blocked fear conditioning to both the tone and the context. MK-801 selectively blocked fear conditioning to the context. Our results support that the ventral hippocampus plays a role in the formation of classical fear conditioning. The specific anterograde amnesia for fear to a context after MK-801 infusion into the ventral hippocampus indicates that formation of classical fear conditioning to a context but not to a tone requires activation of NMDA receptor-mediated processes in the ventral hippocampus. Given that NMDA stimulation of the ventral hippocampus disrupts also processes not mediated by NMDA receptors, the complete anterograde amnesia following NMDA infusion into the ventral hippocampus might be due to the concurrent severe disruption of normal ventral hippocampal activity. However, strong stimulation of the ventral hippocampus might also disrupt fear conditioning by interfering with processes in the projection areas of the ventral hippocampus, such as the amygdala or the nucleus accumbens. In addition, we report that MK-801 (6.25 microg/side) infusion into the ventral hippocampus increased locomotor activity in the open field.

Amygdala↗
PubMed2001

The effects of water deprivation on conditioned freezing to contextual cues and to a tone in rats.

In two experiments we used an automated system for quantifying freezing responses in rats to replicate and extend Maren et al. (Maren S, DeCola JP, Fanselow MS. Water deprivation enhances fear conditioning to contextual, but not discrete, conditional stimuli in rats. Behav Neurosci 1994;108:645-9; Maren S, DeCola JP, Swain RA, Fanselow MS, Thompson RF. Parallel augmentation of hippocampal long-term potentiation, theta rhythm and contextual fear conditioning in water deprived rats. Behav Neurosci 1994;108:44-57) who found that water deprivation in rats produced a selective enhancement in conditioning to context, as opposed to conditioning to a tone. In experiment 1 we gave water deprived and non-deprived rats either three or ten pairings of a tone and foot shock. During conditioning water deprivation decreased overall freezing only in rats that received ten pairings. On 2 subsequent days we assessed conditioned freezing (1) to the contextual cues of the conditioning chamber and (2) to the tone when presented in a distinctive, novel environment. We found, in direct contrast to Maren et al. (Maren S, DeCola JP, Fanselow MS. Water deprivation enhances fear conditioning to contextual, but not discrete, conditional stimuli in rats. Behav Neurosci 1994;108:645-9), that (a) water deprived rats did not differ from non-deprived rats in levels of conditioned contextual freezing and that (b) water deprived rats did show reduced levels of freezing to the tone stimulus. In the same experiment we found that the number of tone-shock pairings did not affect levels of conditioned contextual freezing but that rats that had received three pairings did show reduced levels of freezing to the tone stimulus compared with rats that had received ten pairings, thereby demonstrating that the behavioural procedure and analysis system that we used was appropriately sensitive to differences in conditioning. In experiment 2, therefore, we sought to replicate Maren et al. (Maren S, DeCola JP, Fanselow MS. Water deprivation enhances fear conditioning to contextual, but not discrete, conditional stimuli in rats. Behav Neurosci 1994;108:645-9) using, as far as possible, exactly the same procedural parameters. Here we found that water deprivation produced no effects on conditioned freezing to the contextual cues or to the tone. We conclude that there is sufficient reason to doubt the generality of the previously reported findings.

Acoustic Stimulation↗
PubMed2001

Comparison of the effects of early handling and early deprivation on maternal care in the rat.

It has been reported in the rat that postnatal manipulations can induce robust and persistent effects on offspring neurobiology and behavior, mediated in part via effects on maternal care. There have, however, been few studies of the effects of postnatal manipulations on maternal care. Here, we describe and compare the effects on maternal behavior on postnatal days 1-12 of two manipulations, early handling (EH, 15-min isolation per day) and early deprivation (ED, 4-hr isolation per day), relative to our normal postnatal husbandry procedure. Maternal behavior was measured at five time points across the dark phase of the reversed L:D cycle. EH yielded an increase in arched-back nursing across several time points but did not affect any other behavior. ED stimulated a bout of maternal behavior such that licking and arched-back nursing were increased at the time of dam-litter reunion, although not at any other time point. Neither EH nor ED affected weaning weight significantly. Importantly, within-treatment variation was high relative to these between-treatment effects.

Animals↗
PubMed2001

Effects of psychostimulant withdrawal on latent inhibition of conditioned active avoidance and prepulse inhibition of the acoustic startle response.

RATIONALE: Chronic intermittent administration of amphetamine and cocaine can precipitate psychotic episodes in humans and produce persistent behavioral changes (i.e. increased locomotion, stereotypy) in the rat. The psychostimulant sensitization model of psychosis holds that the repeated administration of drugs such as amphetamine and cocaine induces long-lasting neuroadaptations and behavioral outcomes in animals that parallel aspects of the schizophrenic condition. OBJECTIVES: In the present study, we attempted to validate this model further by examining the effects of short-term withdrawal from repeated administration of cocaine and amphetamine on performance in two animal behavioral models of cognitive deficits found in schizophrenia: latent inhibition and prepulse inhibition. Reductions in both of these behavioral phenomena have been reported in schizophrenic patients and in acutely amphetamine-treated rats. METHODS: Animals were tested after 4 days of withdrawal from 5 days of daily systemic 20 mg/kg cocaine or 1.5 mg/kg amphetamine injections for either latent inhibition of two-way active avoidance acquisition or prepulse inhibition of an acoustic startle response. RESULTS: Our results indicate that, rather than reducing the expression of these behaviors, withdrawal from either cocaine or amphetamine enhanced the expression of latent inhibition of the active avoidance response while having no effect on prepulse inhibition of acoustic startle. CONCLUSIONS: These data indicate that although the sensitized response to amphetamine and cocaine administration may model some aspects of schizophrenic psychosis, behaviors exhibited by sensitized animals in the absence of an acute drug challenge are not consistent with models of the positive symptoms of schizophrenia.

Acoustic Stimulation↗
PubMed2001

Hyperactivity, decreased startle reactivity, and disrupted prepulse inhibition following disinhibition of the rat ventral hippocampus by the GABA(A) receptor antagonist picrotoxin.

RATIONALE: Functional imaging studies have revealed overactivity of the hippocampus in schizophrenic patients. Neuropathological data indicate that hyperactivity of excitatory hippocampal afferents and decreased hippocampal GABA transmission contribute to this overactivity. In rats, excitation of the ventral hippocampus, e.g. by NMDA, results in hyperactivity and disruption of sensorimotor gating measured as prepulse inhibition (PPI) of the acoustic startle response, behavioral effects related to psychotic symptoms in humans. OBJECTIVE: The present study examined whether disinhibition of the ventral hippocampus by the GABA(A) antagonist picrotoxin would result in similar psychosis-related behavioral disturbances (hyperactivity, decreased PPI) as NMDA stimulation. METHODS AND RESULTS: Wistar rats received bilateral infusions of subconvulsive doses of picrotoxin (100 or 150 ng/0.5 microl per side) into the ventral hippocampus and were then immediately tested for open field locomotor activity or startle reactivity and PPI. Only the higher dose induced hyperactivity and decreased PPI. Both doses decreased acoustic startle reactivity to a similar extent. The decreased PPI appeared not to result from decreased startle reactivity, but was associated with a diminished potency of the prepulses to inhibit the startle reaction to the startle pulse, indicating a sensorimotor gating deficit. All effects were temporary, i.e. disappeared when the rats were tested 24 h after infusion. CONCLUSIONS: Decreased GABAergic inhibition in the ventral hippocampus of rats yielded psychosis-related behavioral effects, very similar to those induced by NMDA stimulation. Thus, a concurrence of decreased GABAergic inhibition and increased afferent excitation in the hippocampus of schizophrenic patients might contribute to psychotic symptoms.

Animals↗
PubMed2001

Environmental animal models for sensorimotor gating deficiencies in schizophrenia: a review.

RATIONALE: In schizophrenia research, the study of animal models has received considerable attention in the past 20 years. The value of animal models in pre-clinical research is widely recognised, largely because they can provide precious knowledge regarding the neurobiology of schizophrenia and can also be used for developing antipsychotic drugs. Prepulse inhibition (PPI; reduction in startle reflex induced by a prestimulus) is impaired in schizophrenic patients, a finding that has been associated with a loss of sensorimotor gating abilities. In rats, the schizophrenic-like PPI deficit can be induced by pharmacological or surgical manipulations targeting mainly the cortico-meso-limbic circuitry. OBJECTIVES: The literature was critically reviewed in an effort to determine the robustness and the relevance for schizophrenia of another category of animal models, based purely on manipulations of the social environment, that encompasses the neurodevelopmental hypothesis of schizophrenia. Specifically, we focused our attention on the long-term effects of such environmental models on sensorimotor gating processes as assessed in the PPI paradigm, with an attempt to evaluate their face, predictive and construct validity. RESULTS: Our review of the literature leads to the conclusion that social deprivation performed directly after weaning (approximately 21 days of age) is more likely to be a relevant model for PPI impairments in schizophrenia than pre-weaning manipulations. CONCLUSIONS: Although the robustness of such environmental models requires further study, these animal models offer the advantage of avoiding invasive manipulations, which allows for a variety of anatomical, electrophysiological, neuroendocrine or neurochemical investigations in the absence of confounding pharmacological or surgical effects.

Animals↗
PubMed2001

The ventral hippocampus and fear conditioning in rats. Different anterograde amnesias of fear after tetrodotoxin inactivation and infusion of the GABA(A) agonist muscimol.

Studies on the involvement of the rat hippocampus in classical fear conditioning have focused mainly on the dorsal hippocampus and conditioning to a context. However, the ventral hippocampus has intimate connections with the amygdala and the nucleus accumbens, which are involved in classical fear conditioning to explicit and contextual cues. Consistently, a few recent lesion studies have indicated a role for the ventral hippocampus in classical fear conditioning to explicit and contextual cues. The present study examined whether neuronal activity within the ventral hippocampus is important for the formation of fear memory to explicit and contextual cues by classical fear conditioning. Tetrodotoxin (TTX; 10 ng/side), which completely blocks neuronal activity, or muscimol (1 microg/side), which increases GABA(A) receptor-mediated inhibition, were bilaterally infused into the ventral hippocampus of Wistar rats before the conditioning session of a classical fear-conditioning experiment. Conditioning to a tone and the context were assessed using freezing as a measure of conditioned fear. TTX blocked fear conditioning to both tone and context. Muscimol only blocked fear conditioning to the context. The data of the present study indicate that activity of neurons in the ventral hippocampus is necessary for the formation of fear memory to both explicit and contextual cues and that neurons in the ventral hippocampus that bear the GABA(A) receptor are important for the formation of fear conditioning to a context. In addition, both bilateral muscimol (0.5 microg/side and 1 microg/side) and TTX (5 ng/side and 10 ng/side) infusion into the ventral hippocampus dose-dependently decreased locomotor activity in an open-field experiment.

Acoustic Stimulation↗
PubMed2001

Expression of sensitization to amphetamine and dynamics of dopamine neurotransmission in different laminae of the rat medial prefrontal cortex.

The present study investigated the effect of acute and repeated administrations of amphetamine (AMPH) on dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the two main cytoarchitectonic subterritories of the medial prefrontal cortex (mPFC) (anterior cingulate and dorsocaudal prelimbic cortices vs ventral prelimbic and rostral infralimbic cortices). Both the acute locomotor effects of AMPH and the expression of behavioral sensitization following its repeated administration were also simultaneously assessed. The repeated, intermittent administration of AMPH over five consecutive days led to a significant sensitized locomotor response to a subsequent challenge that occurred following a 48-h withdrawal period. Basal dialysate DA levels were higher in the ventral mPFC compared with its dorsal counterpart in naive animals, that is prior to the acute administration of AMPH. However, the inverse relationship was observed in animals that had developed sensitization: basal dialysate DA levels were significantly lower in the ventral mPFC compared with the dorsal mPFC. In naïve animals, AMPH produced a significant decrease in DA levels in both the ventral and dorsal subregions of the mPFC. However, the inverse relationship was observed in animals that had developed sensitization: dialysate DA levels in response to AMPH remained significantly decreased in the dorsal mPFC, whereas DA went back to baseline levels in the ventral mPFC. Given that a critical concentration of DA is required for normal function of the mPFC, our results suggest that AMPH-induced changes in DA levels in different subregions of the mPFC are critical for both the acute effects of the drug and the expression of behavioral sensitization to its repeated administration by producing either less or more selectivity or sharpening of stimuli to cortico-cortical dendrites and subcortical synaptic afferents to the pyramidal cells located in the dorso-ventral axis of the mPFC.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

An automated analysis of rat behavior in the forced swim test.

The Porsolt forced swim test (FST) is a commonly used paradigm to evaluate antidepressant activity of drugs. This test is based on visual measurement of the rat's floating time (FT) in a tank filled with water. Here, we present an automated, accurate and faster method for estimating FT by the distance moved (DM) by the animal via the use of the Ethovision software in three separate experiments. Experiment 1 investigated the effect of varying delays (24-h and 7-day) between pretest and test on FT and DM. Experiment 2 aimed at examining the effects of a 2-day withdrawal period in rats sensitized to amphetamine and cocaine, on FT and DM. Finally, Experiment 3 looked at the effects of desipramine and fluoxetine on FT and DM. The results of these experiments show that increasing the delay between pretest and test reduced FT during subsequent exposure (test). In addition, rats sensitized to and then withdrawn from either amphetamine or cocaine did not differ in FT or DM compared with control rats. Finally, both desipramine and fluoxetine reduced FT and increased DM. Furthermore, DM was consistently significantly negatively correlated with FT. These results support the use of an automated method for the evaluation of rat behavior in FST.

Amphetamine↗
PubMed2001

Dissociation between the effects of pre-weaning and/or post-weaning social isolation on prepulse inhibition and latent inhibition in adult Sprague--Dawley rats.

Human attentional impairments can be modelled in the rat using the prepulse inhibition (PPI) or the latent inhibition (LI) paradigm. The present study investigated the consequences of a combination of pre-weaning maternal separation (MS) and post-weaning social isolation (SI) on both PPI and LI in male and female Sprague--Dawley rats tested as adults. We report here a double dissociation between the effects of MS (repeated 4 h daily separations) and SI on PPI and LI: MS did not modify PPI, but enhanced LI. In contrast, SI disrupted PPI, the deficits being restricted to male rats, but left LI intact. There were no additive effects of MS and SI on PPI or LI. While MS improved avoidance learning, SI impaired it. Although both PPI and LI assess processes of selective attention, our results support the contention, already stated in the literature, that they involve differing neuro-psychological mechanisms. Furthermore, the fact that only males exhibited PPI deficits following SI has implications for the well-known differential vulnerability of human males to certain psychiatric disorders (e.g. schizophrenia). Finally, the combination of MS and SI could represent a relevant animal model for some aspects of schizophrenia, since both PPI and LI were altered.

Animals↗
PubMed2001

Hyperactivity and disruption of prepulse inhibition induced by N-methyl-D-aspartate stimulation of the ventral hippocampus and the effects of pretreatment with haloperidol and clozapine.

This study re-examined the hyperactivity and disruption of prepulse inhibition induced by N-methyl-D-aspartate stimulation of the rat ventral hippocampus and compared how both effects were affected by pretreatment with either haloperidol or clozapine. While the hyperactivity is thought to depend on dopamine receptor activation in the nucleus accumbens, the dopamine D2-class receptor blocker haloperidol failed to antagonize the disruption of prepulse inhibition in previous studies. However, an ameliorative effect of the atypical neuroleptic clozapine on disruption of prepulse inhibition was suggested by our previous experiments [Zhang et al. (1999) NeuroReport 10, 1-6]. In the present study, bilateral infusion of N-methyl-D-aspartate (0.5microg/side) into the ventral hippocampus of Wistar rats increased open field locomotor activity and disrupted prepulse inhibition. Both effects were observed immediately after infusion but disappeared 24h later. Injection of haloperidol (0.2mg/kg) or clozapine (5mg/kg), 45min prior to N-methyl-D-aspartate infusion, totally antagonized the hyperactivity but did not affect the disruption of prepulse inhibition. We conclude that dopaminergic mechanisms are differentially involved in the hyperactivity and disruption of prepulse inhibition induced by N-methyl-D-aspartate stimulation of the ventral hippocampus. Activation of accumbal dopamine receptors, which is blocked by clozapine and haloperidol to a comparable extent, seems to be crucial for the hyperactivity but not the disruption of prepulse inhibition. The present finding that both clozapine and haloperidol failed to antagonize the disruption of prepulse inhibition induced by N-methyl-D-aspartate stimulation of the ventral hippocampus is discussed with respect to our previous contrary finding concerning the ameliorative effect of clozapine and with respect to the disruption of prepulse inhibition in rats being considered as a model of sensorimotor gating deficits in schizophrenia.

Animals↗
PubMed2001

Differential regulation of chromogranin A, chromogranin B and secretogranin II in rat brain by phencyclidine treatment.

Chromogranin A, chromogranin B and secretogranin II belong to the chromogranin family which consists of large protein molecules that are found in large dense core vesicles. Chromogranins are endoproteolytically processed to smaller peptides. This study was designed to elucidate the regulation of chromgranin expression by acute and subchronic phencyclidine administration. The behavioral syndrome produced by phencyclidine represents a pharmacological model for some aspects of schizophrenia [Jentsch and Roth (1999) Neuropsychopharmacology 20, 201-225]. Tissue concentrations of chromogranins were measured with specific radioimmunoassays. Alterations in secretogranin II gene expression were investigated by in situ hybridization. A single dose of phencyclidine (10mg/kg) led to a transient decrease in secretoneurin tissue levels in the prefrontal cortex after 4h followed by an increase in secretoneurin tissue levels after 12h. Repeated phencyclidine treatment (10mg/kg/day) for five days resulted in elevated secretoneurin levels in cortical areas whereas chromogranin A and chromogranin B tissue levels were unchanged. After the same treatment, a significant increase in the number of secretoneurin containing neurons was found in cortical layers II-III, and V-VI as revealed by immunocytochemistry. The increases in secretoneurin levels were paralleled by an increased number of secretogranin II messenger RNA containing neurons as well as by an increased expression of secretogranin II by individual neurons. The present study shows that secretoneurin II tissue concentration and secretogranin II messenger RNA expression is distinctly altered after acute and subchronic phencyclidine application. From these results we suggest that phencyclidine may induce synaptic alterations in specific brain areas and may contribute to a better understanding of synaptic dysfunction which may also occur in schizophrenia.

Animals↗
PubMed2001

Interactions between environmental stimulation and antipsychotic drug effects on forebrain c-fos activation.

The immediate-early gene product Fos is differentially induced in the rat brain by the antipsychotic drugs haloperidol and clozapine. It is often claimed that although both drugs induce Fos in the nucleus accumbens, haloperidol but not clozapine increases Fos-like immunoreactivity in the striatum, whereas clozapine but not haloperidol increases Fos-like immunoreactivity in prefrontal cortex. Investigations of antipsychotic drug effects on Fos have typically administered high doses with pronounced sedative effects to behaviorally naive animals. In the present study, we compared the effects of low doses of haloperidol (0.1 mg/kg) and clozapine (5 mg/kg) on Fos-like immunoreactivity in rats which were either behaviorally naive, exposed to a novel environment or tested for two-way active avoidance. We determined that haloperidol increased Fos in the striatum and nucleus accumbens regardless of testing condition whereas clozapine markedly reduced the induction of Fos by behavioral testing in these regions; moreover, haloperidol dramatically increased prefrontal cortical Fos expression in animals placed in a novel environment, but not in testing-naive controls. From these results we suggest that antipsychotic drug-induced patterns of Fos expression in the rat are highly dependent on animals' concurrent behavioral status, perhaps reflecting neuroanatomically specific interactions between antipsychotic drugs and environmental stressors which also may occur in the schizophrenic condition.

Animals↗
PubMed2001

Selective responding of nucleus accumbens core and shell dopamine to aversively conditioned contextual and discrete stimuli.

Dopamine transmission within the nucleus accumbens has been implicated as a neurochemical substrate of associative learning processes. It has been suggested that the acquisition of classically conditioned fear to a specific environment, or context, differs fundamentally from the development of conditioned fear to a discrete stimulus, such as a light or a tone. In this study, we assessed extracellular dopamine in the rat nucleus accumbens shell and core during the expression of a conditioned fear response. Animals were aversively conditioned to either a context or a tone and extracellular dopamine was measured in the nucleus accumbens shell and core by in vivo microdialysis over the next 2 days as animals were returned first to the conditioning chamber (day 1: context test), and subsequently as animals were again returned to the chamber and presented with the conditioned tone stimulus (day 2: tone test). Dopamine levels in the core were significantly higher in the Context-Shock group compared to the Tone-Shock group during the 30-min exposure to context while dopamine levels in the nucleus accumbens shell did not differ significantly during the context test between groups. In contrast, extracellular dopamine in the shell but not the core of Tone-Shock animals increased significantly during presentation of the tone. Dopamine in both the shell and core remained unchanged during the tone test in the Context-Shock groups.These data suggest distinct roles for shell and core dopamine transmission in the expression of a conditioned emotional response. While dopamine increased in the shell primarily during the presentation of a discrete tone conditioned stimulus, core dopamine responded more to a contextual conditioned stimulus. These results may reflect differences in either the type of information acquired or the salience of the learned associations which are formed to a context vs. a discrete tone cue.

Acoustic Stimulation↗