Biomedical subjects

Joram Feldon

Publications and source records attributed to Joram Feldon.

At least 55 records · Page 3Linked to original sources

PubMed2005

Double dissociation of the effects of selective nucleus accumbens core and shell lesions on impulsive-choice behaviour and salience learning in rats.

The nucleus accumbens can be subdivided into at least two anatomically distinct subregions: a dorsolateral 'core' and a ventromedial 'shell', and this distinction may extend to a functional dissociation. Here, we contrasted the effects of selective excitotoxic core and medial shell lesions on impulsive-choice behaviour using a delayed reward choice paradigm and a differential reward for low rates of responding (DRL) test, against a form of salience learning known as latent inhibition (LI). Core lesions led to enhanced impulsive choices as evidenced by a more pronounced shift from choosing a continuously reinforced lever to a partially reinforced lever, when a delay between lever press and reward delivery was imposed selectively on the former. The core lesions also impaired performance on a DRL task that required withholding the response for a fixed period of time in order to earn a reward. Medial shell lesions had no effect on these two tasks, but abolished the LI effect, as revealed by the failure of stimulus pre-exposure to retard subsequent conditioning to that stimulus in an active avoidance procedure in the lesioned animals. As expected, selective core lesions spared LI. The double dissociations demonstrated here support a functional segregation between nucleus accumbens core and shell, and add weight to the hypothesis that the core, but not the shell, subregion of the nucleus accumbens is preferentially involved in the control of choice behaviour under delayed reinforcement conditions and in the inhibitory control of goal-directed behaviour.

Animals↗

PubMed2004

Tumor necrosis factor-alpha receptor ablation in a chronic MPTP mouse model of Parkinson's disease.

Recently, we demonstrated that mice deficient of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) were partly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity. Here we extended the study and investigated TNF-alpha receptor 1 (-/-) (TNFR1) and TNF-alpha receptor 2 (-/-) (TNFR2) mice using a chronic MPTP dosing regimen (15 mg/kg MPTP on 8 consecutive days). One week after the last MPTP treatment, HPLC determination of striatal dopamine (DA) and immunostaining for the dopamine transporter (DAT) in the substantia nigra pars compacta (SNpc) was performed. MPTP treatment reduced striatal DA levels significantly; nigral DAT immunoreactivity was reduced to a lower extent. However, there was no difference in DA levels and the number of DAT positive neurons between TNFR1 (-/-), TNFR2 (-/-) and wild type mice after MPTP treatment. In contrast to TNF-alpha deficiency neither TNFR1 nor TNFR2 gene ablation showed protection against MPTP neurotoxicity, which argues for a protective mechanism of TNF-alpha not mediated by TNFR1 and TNFR2 signaling.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2004

Effects of blocking the dopamine biosynthesis and of neurotoxic dopamine depletion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on voluntary wheel running in mice.

In Parkinson's disease (PD) compensatory mechanisms such as an increase of the de novo biosynthesis of dopamine (DA) are thought to delay the onset of motor impairment. Here, we investigated whether the tyrosine hydroxylase (TH) inhibitor alpha-methyl-para-tyrosine (AMPT) affects behavioral deficits in the running wheel activity induced by the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immediately after MPTP treatment C57bl/6 mice showed reduced running wheel activity which lasted during the entire active phase (20:00 to 08:00 h), recovered to baseline levels in the following 2 days and remained stable up to the end of the experiment. AMPT challenge significantly reduced wheel running activity in MPTP-treated mice in the first 3 h after treatment. Post mortem HPLC analysis detected mean striatal DA levels in saline + saline and saline + AMPT-treated mice of 14.32 and 9.83 ng/mg, respectively and in MPTP + saline and MPTP + AMPT-treated mice of 1.73 and 0.69 ng/mg, respectively. Taken together, de novo biosynthesis of DA is a crucial component of the compensatory mechanisms which contributes to masking long-term behavioral deficits in the MPTP mouse model. Additionally, wheel running activity might provide a useful tool to study MPTP-induced behavioral deficits, shifts in circadian rhythmicity, and further compensatory mechanisms relevant to PD.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2004

Acoustic startle response, prepulse inhibition, and spontaneous locomotor activity in MPTP-treated mice.

Parkinson's disease (PD) is marked by characterised motor deficits and is accompanied by a severe degeneration of the nigrostriatal dopamine (DA) pathway. It has also been reported that PD patients exhibited additional behavioural deficits, including a deficiency in sensorimotor gating mechanisms. We therefore examined whether the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD in mice could lead to a sensorimotor gating deficit in the prepulse inhibition (PPI) of the acoustic startle response (ASR) paradigm. Two MPTP treatment schedules were separately examined here in male C57BL/6 mice. Post-mortem HPLC analysis confirmed that they were effective in depleting DA in the dorsal striatum (75-88%). PPI was evaluated on days 2, 9 and 16 after the last MPTP treatment; spontaneous locomotor activity was assessed 24 h before each PPI test. No significant change in the expression of PPI was detected across the three time points. On the other hand, the MPTP treatment reduced activity on post-treatment day 1. This effect subsided on post-treatment day 8, and was reversed on day 15. The possibility remains therefore that the reported sensorimotor gating deficits in PD patients might stem from structural or neurochemical aberrations beyond those induced by MPTP treatment.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2004

Behavioural and cardiovascular responses during latent inhibition of conditioned fear: measurement by telemetry and conditioned freezing.

This study assessed freezing behaviour and cardiovascular responses during the expression of latent inhibition of conditioned fear. Animals that were either repeatedly preexposed (PE) to a tone conditioned stimulus (CS) or naive to the tone (non-preexposed; NPE) subsequently experienced three presentations of the tone paired with footshock. Animals were tested 24 h later in the context of the footshock chamber, and on the following day, in the presence of the tone CS. Changes in heart rate and blood pressure were recorded by radio-telemetry. The PE rats spent more time freezing to the conditioned contextual cues and exhibited higher blood pressures during the last half of the context test session than did the NPE animals. During the tone test, the PE rats exhibited less conditioned freezing to the tone CS compared with the NPE animals, i.e. expression of the latent inhibition. This behavioural effect was associated with a significant increase in heart rate, but not blood pressure, in the PE but not the NPE animals. Our results suggest that the increased blood pressures of the PE rats during the context test directly reflect their greater fear of the conditioning context. In contrast, the increased heart rate response but decreased freezing shown by PE rats in response to the tone CS may be due to the fact that lower stress levels (e.g. PE condition) elicit sympathetically-mediated increases in heart rate, whereas higher stress levels (e.g. NPE condition) activate both sympathetic and parasympathetic systems, thus eliminating any CS-induced increase in heart rate in the NPE rats.

Animals↗

PubMed2004

Deprivation of parenting disrupts development of homeostatic and reward systems in marmoset monkey offspring.

BACKGROUND: Early environment is a major determinant of long-term mental health, evidenced by the relationship between early-life neglect or abuse and chronically increased vulnerability to developmental psychopathology, including major depressive disorder (MDD). Animal studies can increase understanding of environmentally mediated causal risk processes. We describe how daily deprivation of biological parenting in primate infants disrupts development of homeostatic and reward systems central to MDD. METHODS: Nine breeding pairs of marmoset monkeys provided control twins (CON) and early-deprived twins (ED); the latter were socially isolated for 30-120 min/day on days 2-28. During the first year of life, basal urinary norepinephrine (NE) titers and cardiophysiologic activity were measured. At the end of year 1 (adolescence), automated neuropsychologic tests were conducted to measure responsiveness to changes in stimulus-reward association (simple/reversed visual discrimination learning) and to reward per se (progressive ratio [PR] reinforcement schedule). RESULTS: The ED monkeys exhibited increased basal urinary NE titers and increased systolic blood pressure relative to CON siblings. The ED monkeys required more sessions to reinstate stimulus-oriented behavior following reversal, suggesting increased vulnerability to perceived loss of environmental control; ED monkeys also performed less PR operant responses, indicating that reward was less of an incentive and that they were mildly anhedonic relative to CON. CONCLUSIONS: In marmoset monkeys, neglect-like manipulation of ED leads to chronic changes in homeostatic systems, similar to those in children and adolescents exposed to early-life adversity and in MDD, and to responses to environmental stimuli similar to those that characterize MDD.

Animals↗

PubMed2004

Effect of social isolation on stress-related behavioural and neuroendocrine state in the rat.

The present study investigated the effects of post-weaning social isolation (SI) on behavioural and neuroendocrine reactivity to stress of male and female rats. Innate aspects of fear and anxiety were assessed in the open field and elevated plus maze tests. Spontaneous startle reflex and conditioned fear response were further investigated. The neuroendocrine response of isolates was examined by measuring basal and stress release of ACTH and corticosterone and by evaluating the mRNA expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors using in situ hybridization. Locomotor activity in the open field was not modified by chronic SI. In males, but not females, SI produced an anxiogenic profile in the elevated plus maze. Male isolates showed a trend towards increased startle reflex amplitude relative to socially-reared controls. Moreover, SI in males produced alterations of the HPA axis functioning as reflected by higher basal levels of ACTH, and enhanced release of ACTH and corticosterone following stress. In contrast, startle response or HPA axis functioning were not altered in female isolates. Social isolates from both genders showed reduced contextual fear-conditioning. Finally, the mRNA expression of MR and GR was not modified by SI. The results of the present study suggest that chronic SI increases emotional reactivity to stress and produces a hyperfunction of the HPA axis in adult rats, particularly in males.

Adrenocorticotropic Hormone↗

PubMed2004

NMDA lesions in the medial prefrontal cortex impair the ability to inhibit responses during reversal of a simple spatial discrimination.

Although lesion studies suggest that the rat medial prefrontal cortex (mPFc) is involved in the process necessary for reversal of a particular set of contingencies, the nature of lesion-induced deficits is unclear. The involvement of rat mPFc in reversal of a simple spatial discrimination was examined in the present study. Our hypothesis was that lesion-induced deficits may reflect a failure to inhibit a learned instrumental response. Lister Hooded rats were trained on a spatial discrimination task (SD), which required a correct barpress matching the cue location, then they were trained on reversal of SD (SDR), which required a correct barpress opposite to the cue location. Rats with mPFc lesions showed a slower learning rate compared to the controls. However, behavior of the lesioned rats during early and later reversal differed. During the initial SDR, the lesioned rats showed a greater number of barpresses during the intertrial interval and a slightly higher percent correct responses than that of the controls. Our data suggest that damage to mPFc may produce a lack of response inhibition, leading to an increase in nondiscriminated bapresses, thereby yielding a 'facilitation' during early reversal. mPFc lesion did not affect either open field activity or prepulse inhibition (PPI), a frequently used measure of sensorimotor gating. Disruption of reversal learning following damage to mPFc is partly due to a failure to inhibit instrumental responses, rather than to disruption of other processes involved in sensorimotor gating or general activity.

Analysis of Variance↗

PubMed2004

The use of stereological counting methods to assess immediate early gene immunoreactivity.

The issue of whether profile and stereological counting methods are interchangeably accurate when assessing immediate early gene expression still needs to be resolved. To compare these two counting techniques, we quantified the expression of c-fos in the nucleus accumbens core and shell, and in the lateral septum as a control structure, of rats treated with neuroleptics. With the profile counting method, which relies on selective placement of a counting grid within a structure, we evaluated the density of c-fos labeled cells within a box of fixed dimension. With stereology, which applies random and systematic sampling methods, we used the optical fractionator method and counted the absolute number of c-fos labeled cells within the contours of each structure examined. Our results showed that the substantial increase in c-fos expression in the shell and core induced by haloperidol treatment was detected by both stereological and profile counting methods; in contrast, the weaker effect of clozapine on c-fos expression was detected differentially by the two methods. Whereas the profile counting method reported a reduction of c-fos in the core by clozapine, and an increase in c-fos in the lateral septum, these effects were not replicated using stereology. These findings suggest that stereological and profile counting methods do not always produce equivalent results. This may be particularly relevant when a measured effect is relatively small, and it is not distributed homogeneously within a structure. In this respect, the random and systematic sampling methods of stereology may yield more accurate and unbiased results than the profile counting method, and therefore may be preferred for a more accurate and thorough investigation of a treatment effect on immediate early gene expression in a specific brain region.

Analysis of Variance↗

PubMed2004

FAUC 213, a highly selective dopamine D4 receptor full antagonist, exhibits atypical antipsychotic properties in behavioural and neurochemical models of schizophrenia.

RATIONALE: 2-[4-(4-Chlorophenyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine (FAUC 213) is a highly selective antagonist at the dopamine D(4) receptor subtype. It was designed as a derivative of two partial antagonists and has been proven to be a complete antagonist in mitogenesis assay. OBJECTIVES: In the present study, FAUC 213 was examined for antipsychotic properties in animal models of behavioural neurobiology and neurochemistry. METHODS: Different concentrations of FAUC 213 were screened for effects on spontaneous, as well as amphetamine-induced, locomotor activity and apomorphine-induced prepulse disruption. The liability of causing extrapyramidal side effects was investigated in models of catalepsy and by high-performance liquid chromatography (HPLC) detection of dopamine turnover in several brain regions. The application schedule was validated, and the bioavailability of the compound determined, by means of a HPLC-pharmacokinetic study. RESULTS: A significant effect in both the reduction of amphetamine-induced locomotor hyperactivity and the restoration of apomorphine-disrupted prepulse inhibition was found at 30 mg/kg. This dose proved not to be high enough to induce catalepsy or to increase dopamine turnover in the dorsal striatum, nucleus accumbens and medial prefrontal cortex. The selective D(4) antagonist FAUC 213, therefore, is not believed to mediate the above-mentioned effects via D(2) receptor antagonism, but a partial involvement of 5-HT(2)- and alpha(1)-receptors cannot be ruled out at present. CONCLUSIONS: We have gathered evidence that FAUC 213 exhibits atypical antipsychotic characteristics.

Amphetamine↗

PubMed2004

The prenatal methylazoxymethanol acetate treatment: a neurodevelopmental animal model for schizophrenia?

The prenatal methylazoxymethanol acetate (MAM) treatment has been proposed as a suitable model for the neurodevelopmental aspects of schizophrenia since the morphological abnormalities it induces in the brain are subtle and in line with most reports of neuropathology in schizophrenic brains. However, the functional aspects of this treatment have not been investigated with behavioural paradigms that are relevant for the psychopathology of the symptoms of schizophrenia. In the present study, we investigated the validity of the prenatal MAM treatment as a developmental model for schizophrenia with a prepulse inhibition of the acoustic startle reflex, latent inhibition, locomotor activity, and cognition and emotionality with freezing in fear conditioning paradigms. We have conducted two studies: in Study I, MAM was injected from E09 to E12, and in Study II MAM was administered at later stages in the embryonic development, from E12 to E15. Morphologically, the prenatal MAM treatment induced mild to severe reduction in brain weights and in the entorhinal cortex, prefrontal cortex and striatum volumes, the severity of the effects depending on the timing of administration. However, despite the morphological abnormalities induced by the MAM treatments, no behavioural deficits were observed in the MAM-treated animals when compared to Controls in prepulse inhibition, latent inhibition with the two-way active avoidance, and in the freezing paradigms. Therefore, due to the consistent lack of treatment effect observed in the present investigation, we conclude that the prenatal MAM treatment has no validity as a behavioural model for schizophrenia.

Acoustic Stimulation↗

PubMed2004

Circadian- and temperature-specific effects of early deprivation on rat maternal care and pup development: short-term markers for long-term effects?

We compare the effects on pup body weight and on maternal care of 4-hr separation from dam and littermates on postnatal Days 1 to 14 (early deprivation, ED) under different thermal and circadian conditions. ED was performed at either 21 degrees C (Cold), or 32 degrees C (Warm), and either during the light or dark phase. The comparison group was nonhandling (NH), either under a nonreversed (Light) or reversed (Dark) cycle. At weaning, Cold ED pups were of lower body weight than Warm ED pups, and Warm ED pups were of lower body weight than NH pups. Light and Dark ED pups received high care at reunion relative to NH, and Cold ED pups received higher care at several hours postreunion relative to Warm ED and NH pups. We propose that reduced pup weight and increased maternal care are short-term markers for the severity of Cold ED, and that this manipulation could therefore impact negatively on emotionality and cognition in adulthood.

Age Factors↗

PubMed2004

Co-expression of calretinin and gamma-aminobutyric acid in neurons of the entorhinal cortex of the common marmoset monkey.

The gamma-aminobutyric acid (GABA)-containing interneuron population in the entorhinal cortex has been shown to consist of several subpopulations. In addition to GABA, these neurons contain another neurochemical substance, such as a neuropeptide or a calcium binding protein. In the present study, we examined the co-localization of calretinin and GABA in the entorhinal cortex of the common marmoset Callithrix jacchus, a New World monkey. Although the function of calretinin remains unclear, there are indications that it might have a protective role against cell death in a number of neuropathological diseases. Furthermore, it might have a regulatory role in the neurotransmission of GABAergic neurons. In contrast to the rat brain, sparse data exist regarding the degree of co-expression of these two markers in the monkey brain. Using immunofluorescence and confocal laser scanning microscopy, we found that an average of 56% of the calretinin-positive neurons in the monkey entorhinal cortex contained GABA, whereas about 27% of the GABA-positive neurons co-expressed calretinin. Interestingly, these numbers were higher in the superficial layers of the entorhinal cortex in comparison with the deep layers. However, no differences were found in co-localization percentages between the different entorhinal subfields. In general, the degree of co-localization was higher in comparison to findings in the rat entorhinal cortex. The higher amount of co-localization observed in the present study might reflect species differences between the primate and the non-primate brain.

Animals↗

PubMed2004

Performance of the marmoset monkey on computerized tasks of attention and working memory.

The CAmbridge Neuropsychological Test Automated Battery (CANTAB) is a computerised battery of neuropsychological tests presented as stimuli on a touch-sensitive computer screen that has been used to assess a wide range of cognitive functions in neuropsychiatric patients, healthy volunteers, and species of non-human primate, primarily the rhesus macaque. The common marmoset is a small-bodied, tractable simian primate that breeds well under laboratory conditions. This primate has been quite extensively studied in terms of its abilities and limitations with respect to appetitive cognitive conditioning. However, the CANTAB versions of sustained/divided attention and working memory tasks have to-date not been studied in the marmoset. Here we describe adult marmoset performance on the CANTAB five-choice serial reaction time task, a delayed match-to-position task, and a task derived from the CANTAB visuo-spatial paired associates learning task that constituted two, concurrent delayed match-to-position tasks. The acquisition and stable longitudinal performance of these tasks provide strong evidence that the marmoset, in addition to the macaque, can be the species of choice for CANTAB-based drug and lesion studies of cognitive function, using tasks similar to those deployed in the study of human cognition and diagnosis of neuropsychiatric disorders.

Animals↗

PubMed2004

Long-term social isolation and medial prefrontal cortex: dopaminergic and cholinergic neurotransmission.

Rearing rats in social isolation has been suggested as an animal model of schizophrenia, based mainly on the similarity between the attenuation of prepulse inhibition (PPI) in isolated rats and in schizophrenic patients. The medial prefrontal cortex (mPFC) plays a major role in the pathophysiology of schizophrenia. Thus, a postmortem micropunch analysis measuring dopamine (DA), DOPAC (3,4-dihydroxyphenylacetic acid) and homovanillic acid (HVA) in the dorsal and ventral subregion of the mPFC, the caudate putamen (CPu) and nucleus accumbens (NAc) was carried out on socially isolated or group-housed male Sprague-Dawley (SD) rats. Additionally, in vivo microdialysis with D-amphetamine (1 mg/kg ip) stimulation was performed in isolated animals and their controls, examining the ventral mPFC for acetylcholine (ACh), DOPAC and HVA levels. Simultaneously, recording of motor activity was performed. In the neurochemical postmortem tissue analysis we found no difference in any of the brain regions tested between isolated and group-reared animals. Amphetamine increased ACh levels in the mPFC, induced a decrease in DOPAC and HVA levels, and increased motor activity. A close to significant Drug x Housing interaction reflected the fact that the amphetamine-induced decrease of DOPAC was confined to the group-housed animals. In conclusion, social isolation leads only to moderate changes in the dopaminergic system in the mPFC, whereas the cholinergic system remains unaffected.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2004

Development of acute withdrawal during periodic administration of amphetamine in rats.

Amphetamine (AMPH) administration appears to produce multiple time-dependent effects during the approximately 24-h period after administration. This study examined the development of these effects. Rats were housed in separate cubicles, had ad-lib access to food and water, and were continuously monitored. After a series of control treatments, different groups received AMPH (1.0 mg/kg ip) at either 33- or 24-h intervals. Light-dark cycles (12-12 h) were "staggered" by 3-h intervals across the rats in each group, so that the effects of AMPH could be readily detected in average activity profiles against the background of light-entrainable activity. Changes in activity indicated that AMPH produced a common sequence of effects on both 33- and 24-h-period schedules: psychomotor stimulation (Hours 1-3 postdrug), withdrawal (activity suppression near Hour 20 postdrug), and recovery (activity increase beginning around Hour 24 postdrug). Withdrawal and recovery effects developed during the first several AMPH administration cycles. These time-dependent changes during the approximately 24-h interval after AMPH administration could reflect changes in motivation and in susceptibility to processes thought to underlie the acquisition of drug abuse (such as the positive and negative reinforcing effects of drug receipt). Short- and long-term responsiveness to drug might then depend on when in the postdrug sequence administrations occur.

Acute Disease↗

PubMed2004

Mesolimbic dopaminergic pathways in fear conditioning.

One of the most common paradigms used to study the biological basis of emotion, as well as of learning and memory, is Pavlovian fear conditioning. In the acquisition phase of a fear conditioning experiment, an emotionally neutral conditioned stimulus (CS)--which can either be a discrete stimulus, such as a tone, or a contextual stimulus, such as a specific environment--is paired with an aversive unconditioned stimulus (US), for example a foot shock. As a result, the CS elicits conditioned fear responses when subsequently presented alone during the expression phase of the experiment. While considerable work has been done in relating specific circuits of the brain to fear conditioning, less is known about its regulation by neuromodulators; the understanding of which would be of therapeutic relevance for fear related diseases such as phobia, panic attacks, post traumatic stress disorder, obsessive compulsive disorder, or generalized anxiety disorder. Dopamine is one of the neuromodulators most potently acting on the mechanisms underlying states of fear and anxiety. Recently, a growing body of evidence has suggested that dopaminergic mechanisms are significant for different aspects of affective memory, namely its formation, expression, retrieval, and extinction. The aim of this review is to clarify the complex actions of dopamine in fear conditioning with respect to the wide-spread distribution of dopaminergic innervation over structures constituting the fear related circuitry. A particular effort is made to understand how dopamine in the amygdala, medial prefrontal cortex and nucleus accumbens--target structures of the mesolimbic dopamine system originating from the ventral tegmental area--could relate to different aspects of fear conditioning.

Animals↗

PubMed2004

Apomorphine-induced prepulse inhibition disruption is associated with a paradoxical enhancement of prepulse stimulus reactivity.

Prepulse inhibition (PPI) refers to the reduction in startle reaction to a startle-eliciting stimulus when it is shortly preceded by a subthreshold prepulse stimulus. PPI has been extensively employed as an assay for sensorimotor gating, and its disruption has been characterized in specific disease conditions, including schizophrenia. In animals, dopamine agonists disrupt PPI, and this disruption can be antagonized by antipsychotic drug treatment. The present study extended these fundamental findings to C57BL6 mice, and further evaluated the subjects' reaction to the prepulse stimulus alone in relation to the expression of PPI. Not only did apomorphine (2.0 mg/kg, intraperitoneal (i.p.)) attenuate PPI but it also enhanced reactivity to the prepulse stimulus. The dual effects of apomorphine appear paradoxical in view of the positive correlation, detectable in both the control and apomorphine groups, between prepulse reactivity and PPI magnitude. The present findings contradict the hypothesis that apomorphine disrupts PPI via reduced detectability or perception of the prepulse, and we further propose that enhanced distractibility may provide a parsimonious account for the dual effects of apomorphine. Moreover, haloperidol pretreatment (0.4 mg/kg, i.p.) fully antagonized the effects of apomorphine upon prepulse reactivity as well as on PPI. The present results add to our understanding of the relevance and applicability of the PPI paradigm in modeling schizophrenia-like symptoms in animals.

Acoustic Stimulation↗