Biomedical subjects

Joram Feldon

Publications and source records attributed to Joram Feldon.

At least 19 recordsLinked to original sources

PubMed2007

Effects of prenatal dexamethasone treatment on postnatal physical, endocrine, and social development in the common marmoset monkey.

The prophylactic treatment of diagnosed preterm delivery with synthetic glucocorticoids, such as dexamethasone (DEX), is commonplace. Long-term effects of such treatment are not well understood. In the present study, we exposed pregnant common marmosets (Callithrix jacchus), small-bodied monkeys that are therefore advantageous for long-term primate studies, to daily repeated DEX (5 mg/kg orally) either during early (d 42-48) or late (d 90-96) pregnancy (gestation period of 144 d). Relative to control, we investigated DEX effects in terms of maternal endocrinology (plasma cortisol and estrogen titers) and offspring physical growth, plasma and urinary ACTH and cortisol titers, and social and maintenance behaviors from birth to weaning. Both DEX treatments resulted in markedly reduced maternal plasma cortisol titers during treatment and reduced estimated gestation period. Both treatments were without effects on neonate morphometric measurements and basal hypothalamic-pituitary-adrenal axis activity. Early DEX treatment resulted in increased infant body weight at postnatal d 56 and 84, co-occurring at the behavioral level with increased time spent in eating solid food, a mobile state, solitary play, and exhibiting tail hair piloerection. The constellation of physical and behavioral effects of early DEX suggests interesting parallels with the human metabolic syndrome, providing primate support that the latter is causally associated with the fetal environment, including prenatal programming. This novel primate in vivo evidence for postnatal effects of prenatal synthetic glucocorticoid exposure indicates the importance of improved understanding of this acute clinical treatment in terms of its long-term effects on offspring well-being.

Animals↗

PubMed2006

Disruption of the US pre-exposure effect and latent inhibition in two-way active avoidance by systemic amphetamine in C57BL/6 mice.

RATIONALE: Pre-exposure to either one of the two to-be-associated stimuli alone is known to reduce the efficiency of the learning of their association when they are subsequently paired explicitly. In classical conditioning, pre-exposure to the conditioned stimulus (CS) gives rise to latent inhibition (LI); and pre-exposure to the unconditioned stimulus (US) results in the US pre-exposure effect (USPEE). Considerable evidence supports an important role of central dopamine in the regulation and modulation of LI; it has been suggested that the USPEE may be similarly controlled by dopamine, but this parallelism has only been directly demonstrated in the conditioned taste aversion paradigm. OBJECTIVE: The present study tested this hypothesis by comparing the efficacy of systemic amphetamine treatment to affect the expression of LI and the USPEE in a two-way active avoidance paradigm. METHODS: C57BL/6 male mice were tested in active avoidance using a tone CS and a foot-shock US. Twenty-four hours before, they were pre-exposed to 100 presentations of the CS or the US, or to the test apparatus only. Amphetamine (2.5 mg/kg) or saline was administered before stimulus pre-exposure and conditioned avoidance test, in which the mice learned to avoid the shock by shuttling in response to the tone. RESULTS: Amphetamine disrupted both stimulus pre-exposure effects, thus, lending further support to the hypothesis that the USPEE is similar to LI in its sensitivity to dopamine receptor agonist. Hence, the USPEE paradigm may represent a valuable addition to the study of dopamine-sensitive processes of selective learning currently implicated in LI and Kamin blocking.

Amphetamine↗

PubMed2006

Prenatal dexamethasone exposure, postnatal development, and adulthood prepulse inhibition and latent inhibition in Wistar rats.

Prenatal stress is an important risk factor in schizophrenia, and the aetiological factors mediating this relationship are central to the neurodevelopmental hypothesis of schizophrenia. The glucocorticoid receptor (GR) agonist dexamethasone (DEX) is commonly prescribed for prenatal conditions, and results in GR activation, which is part of the stress response. To investigate animal evidence for whether prenatal DEX leads to development of schizophrenia-like phenotypes, Wistar rats were prenatally exposed to DEX (0.1mg/kg/day) between the gestational days 15 and 21, and tested in two paradigms known to be disrupted in schizophrenia patients: prepulse inhibition (PPI) and latent inhibition (LI). A cross-fostering design was used to allow dissociation of any direct prenatal effects on offspring from effects dependent on DEX exposure of the rearing dam. Pup birth weight was reduced by prenatal DEX treatment. DEX-treated dams demonstrated increased pup-directed behaviour. There were additive effects of prenatal DEX treatment and DEX treatment of rearing dam in terms of reduced body weight in adulthood. In one of two replications, PPI was increased by prenatal DEX in males only and specific to the highest prepulse intensity. There was no evidence that LI was disrupted by prenatal DEX treatment. This study does not provide support for the hypothesis that prenatal DEX exposure leads to schizophrenia-like deficits in PPI or LI, suggesting that GR prenatal programming is not a mechanism of direct relevance to the neurodevelopmental hypothesis of schizophrenia.

Acoustic Stimulation↗

PubMed2006

The monotonic dependency of prepulse inhibition of the acoustic startle reflex on the intensity of the startle-eliciting stimulus.

Prepulse inhibition (PPI) of the acoustic startle reflex is a translational behavioural paradigm for the assessment of sensorimotor gating deficit which has been demonstrated in a number of neuropsychiatric conditions. PPI refers to the reduction of the reflexive startle response to a 'pulse' stimulus when its presentation is shortly preceded by a weak 'prepulse' stimulus. We have recently examined the expression of PPI as a function of the startle-eliciting 'pulse' stimulus intensity in mice and in humans. One major discrepancy that emerged was the finding that healthy human subjects, unlike normal mice, did not show a clear monotonic reduction of PPI magnitude (as indexed by % reduction in startle reactivity) with increasingly intense pulse stimulus. This lack of correspondence between species may potentially weaken the translational power of the PPI paradigm. Here, we re-examined this issue in 31 healthy subjects across three levels of pulse stimulus intensity (95, 105 and 115 dB). A clear linear reduction of PPI as a function of pulse intensity was revealed when subjects failing to respond to the lowest pulse stimulus were excluded. Inclusion of such non-responders, on the other hand, resulted in a trend towards an inverted U-shape function as reported previously. The present study thus clarifies an apparent divergence between mouse and man, and provides important qualification to the "First Law of Reflex Modification" proposed by Hoffman and Ison which suggests that the absolute reduction in startle reactivity resulting from a prepulse stimulus preceding the startle-eliciting pulse stimulus is fixed by the prepulse intensity regardless of the pulse stimulus intensity.

Acoustic Stimulation↗

PubMed2006

Effects of dorsal and ventral hippocampal NMDA stimulation on nucleus accumbens core and shell dopamine release.

This study has analysed the effects of infusing N-methyl-D-aspartate (NMDA) into either the ventral or dorsal hippocampus on dopamine (DA) transmission in the nucleus accumbens (NAC) core or shell for the first time. Dopamine was measured using in vivo microdialysis with high performance liquid chromatography with electrochemical detection (HPLC-EC). Unilateral NMDA infusion (0.5 microg) into the ventral hippocampus (VH) increased extracellular DA levels in NAC shell during the first 30 min following infusion compared to saline (SAL) infused animals. In contrast, NAC core DA levels were unaffected. NMDA infusion into the dorsal hippocampus (DH) led to a decrease in NAC core DA levels; this effect was not observed in the SAL-infused group. DA levels in NAC shell remained unaltered. At the end of the experiments, we examined the response to a systemic amphetamine (AMPH) injection of 1mg/kg on extracellular DA levels of the NAC core and shell. Interestingly, on2ly animals previously infused with NMDA into the VH exhibited a sensitized DA response in the NAC shell in response to the AMPH injection. We can conclude that VH activation has an acute stimulatory effect on DA release in the shell and that DH activation has a suppressive effect on extracellular DA levels in the core.

Amphetamine↗

PubMed2006

Enhancing effects of nicotine and impairing effects of scopolamine on distinct aspects of performance in computerized attention and working memory tasks in marmoset monkeys.

With the CAmbridge Neuropsychological Test Automated Battery (CANTAB), computerized neuropsychological tasks can be presented on a touch-sensitive computer screen, and this system has been used to assess cognitive processes in neuropsychiatric patients, healthy volunteers, and species of non-human primate, primarily the rhesus macaque and common marmoset. Recently, we reported that the common marmoset, a small-bodied primate, can be trained to a high and stable level of performance on the CANTAB five-choice serial reaction time (5-CSRT) task of attention, and a novel task of working memory, the concurrent delayed match-to-position (CDMP) task. Here, in order to increase understanding of the specific cognitive demands of these tasks and the importance of acetylcholine to their performance, the effects of systemic delivery of the muscarinic receptor antagonist scopolamine and the nicotinic receptor agonist nicotine were studied. In the 5-CSRT task, nicotine enhanced performance in terms of increased sustained attention, whilst scopolamine led to increased omissions despite a high level of orientation to the correct stimulus location. In the CDMP task, scopolamine impaired performance at two stages of the task that differ moderately in terms of memory retention load but both of which are likely to require working memory, including interference-coping, abilities. Nicotine tended to enhance performance at the long-delay stage specifically but only against a background of relatively low baseline performance. These data are consistent with a dissociation of the roles of muscarinic and nicotinic cholinergic receptors in the regulation of both sustained attention and working memory in primates.

Acetylcholine↗

PubMed2006

The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology.

Disturbance to early brain development is implicated in several neuropsychiatric disorders including autism, schizophrenia, and mental retardation. Epidemiological studies have indicated that the risk of developing these disorders is enhanced by prenatal maternal infection, presumably as a result of neurodevelopmental defects triggered by cytokine-related inflammatory events. Here, we demonstrate that the effects of maternal immune challenge between middle and late gestation periods in mice are dissociable in terms of fetal brain cytokine responses to maternal inflammation and the pathological consequences in brain and behavior. Specifically, the relative expression of pro- and anti-inflammatory cytokines in the fetal brains in response to maternal immune challenge may be an important determinant among other developmental factors for the precise pathological profile emerging in later life. Thus, the middle and late gestation periods correspond to two windows with differing vulnerability to adult behavioral dysfunction, brain neuropathology in early adolescence, and of the acute cytokine responses in the fetal brain.

Analysis of Variance↗

PubMed2006

Amphetamine withdrawal leads to behavioral sensitization and reduced HPA axis response following amphetamine challenge.

Withdrawal from repeated amphetamine (AMPH) administration leads to behavioral sensitization following a drug or a stress challenge and is commonly used to model anhedonia in rats, a core symptom of depression in humans. It is proposed that corticosteroids are involved in the mediation of sensitization and depression. The aim of the present study was to investigate stress and AMPH- induced release of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) during withdrawal from an escalating dosage schedule of AMPH known to produce depression-like effects in rats. Wistar rats were given 3 injections (i.p.) per day over 3 days, escalating from 1 mg/kg to 9 mg/kg and a final injection of 10 mg/kg AMPH or saline on day 4. On day 2 of withdrawal, the animals were tested in the Porsolt swim test. HPA axis activity in response to restraint stress was tested on withdrawal day 14 and in response to AMPH challenge on withdrawal day 30. We found no effect of AMPH withdrawal in the Porsolt swim test and on the ACTH or CORT response following restraint stress. AMPH withdrawn animals expressed behavioral sensitization in terms of locomotion and reduced ACTH and CORT plasma levels following a 1 mg/kg AMPH challenge in comparison to the controls. We conclude that there is no critical involvement of a sensitized HPA axis stress response in the long-term expression of behavioral sensitization.

Adrenocorticotropic Hormone↗

PubMed2006

Prenatal and postnatal maternal contributions in the infection model of schizophrenia.

Epidemiological studies have indicated that the risk of schizophrenia is enhanced by prenatal maternal infection with viral or bacterial pathogens. Recent experimentation in rodents has yielded additional support for a causal relationship between prenatal immune challenge and the emergence of psychosis-related abnormalities in brain and behaviour in later life. However, little is known about the putative roles of maternal postnatal factors in triggering and modulating the emergence of psychopathology following prenatal immunological stimulation. Here, we aimed to dissect the relative contributions of prenatal inflammatory events and postnatal maternal factors in precipitating juvenile and adult psychopathology in the resulting offspring with a cross-fostering design. Pregnant mice were exposed to the viral mimic, polyriboinosinic-polyribocytidilic acid (PolyI:C; at 5 mg/kg, intravenously), or vehicle treatment on gestation day 9, and offspring born to PolyI:C- and vehicle-treated dams were then simultaneously cross-fostered to surrogate rearing mothers, which had either experienced inflammatory or vehicle treatment during pregnancy. Prenatal PolyI:C administration did not affect the expression of latent inhibition (LI) at a juvenile stage of development, but led to the post-pubertal emergence of LI disruption in both aversive classical and instrumental conditioning regardless of the postnatal rearing condition. In addition, deficits in conditioning as such led to a pre- and post-pubertal loss of LI in prenatal control animals that were adopted by PolyI:C-treated surrogate mothers. Our findings thus indicate that the adoption of prenatally immune-challenged neonates by control surrogate mothers does not possess any protective effects against the subsequent emergence of psychopathology in adulthood. At the same time, however, the present study highlights for the first time that the adoption of prenatal control animals by immune-challenged rearing mothers is sufficient to precipitate learning disabilities in the juvenile and adult offspring.

Acoustic Stimulation↗

PubMed2006

Disruption of glycine transporter 1 restricted to forebrain neurons is associated with a procognitive and antipsychotic phenotypic profile.

The NMDA receptor is thought to play a central role in some forms of neuronal plasticity, including the induction of long-term potentiation. NMDA receptor hypofunction can result in mnemonic impairment and has been implicated in the cognitive symptoms of schizophrenia. The activity of NMDA receptors is controlled by its endogenous coagonist glycine, and a local elevation of glycine levels is expected to enhance NMDA receptor function. Here, we achieved this by the generation of a novel mouse line (CamKIIalphaCre;Glyt1tm1.2fl/fl) with a neuron and forebrain selective disruption of glycine transporter 1 (GlyT1). The mutation led to a significant reduction of GlyT1 and a corresponding reduction of glycine reuptake in forebrain samples, without affecting NMDA receptor expression. NMDA (but not AMPA) receptor-evoked EPSCs recorded in hippocampal slices of mutant mice were 2.5 times of those recorded in littermate controls, suggesting that neuronal GlyT1 normally assumes a specific role in the regulation of NMDA receptor responses. Concomitantly, the mutants were less responsive to phencyclidine than controls. The mutation enhanced aversive Pavlovian conditioning without affecting spontaneous anxiety-like behavior in the elevated plus maze and augmented a form of attentional learning called latent inhibition in three different experimental paradigms: conditioned freezing, conditioned active avoidance, conditioned taste aversion. The CamKIIalphaCre;Glyt1tm1.2fl/fl mouse model thus suggests that augmentation of forebrain neuronal glycine transmission is promnesic and may also offer an effective therapeutic intervention against the cognitive and attentional impairments characteristic of schizophrenia.

Animals↗

PubMed2006

Withdrawal from continuous amphetamine administration abolishes latent inhibition but leaves prepulse inhibition intact.

RATIONALE: Schizophrenia has been associated with dysregulation of dopamine (DA) transmission and impairment in a number of experimental tasks, including sensorimotor gating assessed using prepulse inhibition (PPI) and selective attention assessed using latent inhibition (LI). We have demonstrated in previous studies that after withdrawal from escalating (ESC) dosages of amphetamine (AMPH), animals exhibited disruption of LI but no alteration of PPI. Moreover, these animals always showed behavioural sensitization to an AMPH challenge. OBJECTIVE: In this study, we were interested in testing whether a different administration schedule would elicit disruption of both LI and PPI. METHODS: Animals were treated with continuous AMPH release (via osmotic mini-pumps at a dosage of 10 mg kg(-1) day(-1) for 7 days) and tested for their performance in L and PPI during withdrawal in a drug free state. Rats received AMPH treatment during the induction phase in their home cages or in the activity chambers. Following withdrawal, the expression of behavioural sensitization to an AMPH challenge was tested in both cases in the activity chambers. RESULTS: Animals pretreated with AMPH from both groups did not exhibit behavioural sensitization. Withdrawal from continuous administration induced LI attenuation with no effect on PPI. CONCLUSIONS: These findings are similar to what was previously found with respect to an ESC AMPH regime. The only difference between the schedules was that the ESC AMPH schedule led to behavioural sensitization whereas the continuous AMPH did not. It is suggested that the expression of sensitization may not be a prerequisite for observed LI disruption.

Acoustic Stimulation↗

PubMed2006

Differential effects on prepulse inhibition of withdrawal from two different repeated administration schedules of amphetamine.

In this study, rats were tested in behavioural paradigms relevant to schizophrenia during withdrawal from two different administration schedules of amphetamine (Amph). One of the escalating administration schedules, which has been employed in previous studies, consisted of three daily injections for 6 d with increasing dosages from 1 to 5 mg/kg Amph (Esc-5) and was compared to a hitherto never examined escalating administration schedule [three injections per day for 6 d escalating from 1 to 8 mg/kg Amph (Esc-8)]. Control animals received an equivalent volume of saline (Sal) injections according to the same schedule. Whereas rats treated with Esc-5, as reported before, failed to show an effect on prepulse inhibition (PPI), the Esc-8-treated rats exhibited a long-lasting disruption of PPI in a drug-free state on days 6, 13 and 55 of withdrawal. The Amph-pretreated animals demonstrated a similar magnitude of behavioural sensitization following an Amph challenge on withdrawal day 58 irrespective of the administration schedule. To evaluate if the withdrawal from the two Amph schedules led to a change in brain monoamine levels, a subgroup of animals was neurochemically examined in post-mortem for eight parameters in seven brain regions on withdrawal day 55. Withdrawal from the Esc-8 schedule induced reduced dopamine levels in the caudate putamen. Only this neurochemical finding and the PPI attenuation differentiated the Esc-8 animals from the Esc-5 and Sal animals. These data suggest that, based on the endogenous sensitization hypothesis of schizophrenia, the persistent disruption of PPI observed in animals withdrawn from Esc-8 can be used as a valid animal model of specific symptoms of schizophrenic patients.

Animals↗

PubMed2006

Facilitated extinction of appetitive instrumental conditioning following excitotoxic lesions of the core or the medial shell subregion of the nucleus accumbens in rats.

The nucleus accumbens has been implicated in the control of goal-directed behaviour, including instrumental conditioning. Here, we evaluated the effect of N-methyl-D: -aspartate (NMDA)-induced excitotoxic lesions restricted to either the core or the medial shell subregions of the nucleus accumbens (NAC) on extinction in rats using a trial discrete fixed ratio-5 (FR-5) appetitive operant procedure. Neither core nor shell lesions of the NAC affected the acquisition of instrumental responding. Both lesions facilitated the cessation of responding when the instrumental act no longer yielded reinforcement. Our results suggest that both the NAC core and medial shell contribute to the control of extinction learning of appetitively motivated instrumental behaviour.

Analysis of Variance↗

PubMed2006

Influence of differential housing on emotional behaviour and neurotrophin levels in mice.

Environmental enrichment condition (EC) induces profound behavioural, neurochemical and neuroanatomical changes. Increasing evidence has shown that the hippocampus, which is implicated in a range of cognitive functions, including learning and memory, is one of the most susceptible brain areas to the effects of enriched rearing. Recent work also suggests that the hippocampus is functionally segregated; lesion studies have shown that the dorsal hippocampus is important for spatial learning, whereas the ventral part is critical in emotional behaviour in rats. We investigated the effects of differential housing environments on anxiety-related behaviour and neurotrophin levels in dorsal and ventral hippocampus, and other brain regions. Ninety-six male and female C57BL/6 mice were reared in EC or standard housing condition (SC) for 4 months after weaning. Thereafter sixty-four animals were tested in the elevated plus-maze, open-field, novel-objects exploration and food neophobia. Thirty-two animals remained as untested. Subsequently, brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were analysed in selected brain regions of the tested and non-tested animals. Differential housing influenced anxiety-related behaviour in the plus-maze and brain neurotrophins. Baseline levels of BDNF and NGF protein were differently distributed in dorsal and ventral parts of hippocampus in both male and female mice, with levels in the dorsal hippocampal being consistently higher than those in ventral hippocampus. Exposure to behavioural testing induced complex changes on neurotrophin levels in selected brain regions. This study demonstrates for the first time the differential distribution of normal levels of neurotrophin protein in dorsal and ventral hippocampus in mice, and these levels can be affected by environmental enrichment and have an impact on emotional behaviour.

Analysis of Variance↗

PubMed2006

The International Society for Developmental Psychobiology annual meeting symposium: Impact of early life experiences on brain and behavioral development.

Decades of research in the area of developmental psychobiology have shown that early life experience alters behavioral and brain development, which canalizes development to suit different environments. Recent methodological advances have begun to identify the mechanisms by which early life experiences cause these diverse adult outcomes. Here we present four different research programs that demonstrate the intricacies of early environmental influences on behavioral and brain development in both pathological and normal development. First, an animal model of schizophrenia is presented that suggests prenatal immune stimulation influences the postpubertal emergence of psychosis-related behavior in mice. Second, we describe a research program on infant rats that demonstrates how early odor learning has unique characteristics due to the unique functioning of the infant limbic system. Third, we present work on the rodent Octodon degus, which shows that early paternal and/or maternal deprivation alters development of limbic system synaptic density that corresponds to heightened emotionality. Fourth, a juvenile model of stress is presented that suggests this developmental period is important in determining adulthood emotional well being. The approach of each research program is strikingly different, yet all succeed in delineating a specific aspect of early development and its effects on infant and adult outcome that expands our understanding of the developmental impact of infant experiences on emotional and limbic system development. Together, these research programs suggest that the developing organism's developmental trajectory is influenced by environmental factors beginning in the fetus and extending through adolescence, although the specific timing and nature of the environmental influence has unique impact on adult mental health.

Animals↗

PubMed2006

The role of voluntary exercise in enriched rearing: a behavioral analysis.

The effects of postweaning enriched rearing and home cage voluntary wheel-running exercise in adulthood were contrasted on a comprehensive battery of tests designed to assess mnemonic, attentional, emotional, and motor functions. In a 2 x 2 factorial design, female C57BL/6 mice were housed in groups in either standard or enriched cages, which were equipped with either a running or a locked wheel. They were maintained in the corresponding housing conditions for 2 months postweaning prior to, and throughout, testing. Enriched rearing was associated with anxiogenesis, hypolocomotor activity, enhanced motor skills, retarded extinction of conditioned responding, and improved water maze performance. Exercise as such enhanced motor coordination and facilitated extinction of contextual conditioning. Evidence for an interaction between enrichment and exercise was apparent in the open field test, conditioned freezing to a tone stimulus, prepulse inhibition, and acquisition of water maze reference memory. Hence, care should be taken to control for the unique contribution of wheel-running exercise when it is included as an integral component of the enrichment procedure.

Analysis of Variance↗

PubMed2006

Use of the elevated plus-maze test with opaque or transparent walls in the detection of mouse strain differences and the anxiolytic effects of diazepam.

The elevated plus-maze is a widely employed behavioural assay for anxiolytic and anxiogenic agents in rodents. Among laboratories, however, the apparatus often differs between the use of transparent and opaque walls. This inconsistency may represent an unnecessary confound in the literature when comparing results. Here, we directly contrasted the two designs with respect to (1) mouse strain differences (C57BL/6, 129/Sv, and C3H/He) and (2) sensitivity to diazepam (0.5, 1.0, and 1.5 mg/kg, intraperitoneal). Both mazes yielded similar results indicating that 129/Sv mice were more anxious than C57BL/6 or C3H mice, with the transparent elevated plus-maze tending to encourage open-arm exploration in all three strains. Next, we examined the effect of diazepam in the 129/Sv strain across the two mazes. Systemic diazepam at 1.5 mg/kg led to increased percentage time spent in the open arms in both elevated plus-mazes; the drug was ineffective in both elevated plus-mazes at a dose of 0.5 mg/kg. Although our results revealed little practical difference between the two mazes in terms of their ability to detect differences in anxiety-related behaviour, the baseline difference in open-arm exploration between the two elevated plus-mazes suggests that the transparent design may be more congenial for the detection of anxiogenic manipulations, and the opaque maze for anxiolytic manipulations.

Animals↗

PubMed2006

Selective nucleus accumbens core lesions enhance dizocilpine-induced but not apomorphine-induced disruption of prepulse inhibition in rats.

Prepulse inhibition refers to the reduction in startle reaction to a startle-eliciting 'pulse' when it is shortly preceded by a weak 'prepulse' stimulus. The nucleus accumbens plays a pivotal role in the regulation of prepulse inhibition in rats, but the relative contributions of its subregions remain unclear. Here, we investigated the effects of selective excitotoxic lesion restricted to the nucleus accumbens core on prepulse inhibition and its sensitivity to dopaminergic and glutamatergic manipulations known to disrupt prepulse inhibition. We first assessed the effects of selective core lesions on prepulse inhibition, before going on to evaluate whether the lesions affect the sensitivity to the prepulse inhibition-disruptive effects of systemic treatment of the dopamine agonist, apomorphine (0.025 mg/kg, subcutaneous) and of the non-competitive N-methyl-D-aspartate receptor antagonist, dizocilpine (0.1 mg/kg, subcutaneous). Contrary to our expectations, core lesions failed to disrupt prepulse inhibition. The lesions, however, enhanced the disruptive effect of dizocilpine, but not of apomorphine, on prepulse inhibition. Our results thus suggest that nucleus accumbens core can indeed lead to deregulation of prepulse inhibition, perhaps via a disturbance of normal glutamatergic activity.

Animals↗