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

The Lewis (LEW) and Fischer (F344) rat strains provide a comparative model of hypothalamic-pituitary-adrenal (HPA) function in which LEW is relatively hypoactive at homeostasis and hyporeactive to environmental challenge. The present study describes a comparison of LEW and F344 rats, males and females, in terms of their corticosterone (CORT) or behavioural responses to a range of behavioural tasks, where each of the tasks used contains a stressor component and has been demonstrated to be sensitive to corticotropin releasing factor (CRF) and/or CORT manipulation: acoustic startle response (ASR), elevated plus maze, schedule-induced polydipsia, and fear-conditioned suppression of drinking. Our aim was to determine to what extent the LEW trait of HPA axis hyporesponsiveness is associated with strain differences in behavioural responsiveness to environmental challenge.

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.

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

Disruption of prepulse inhibition (PPI) induced by NMDA receptor antagonists, such as MK801, has been used as an animal model of positive and negative symptoms of schizophrenia. Previous studies suggested that atypical, but not typical, neuroleptics can selectively restore MK801-induced PPI disruption and that such selectivity may depend on strain differences. The present study re-examined PPI disruption by systemic MK801 in Wistar (WS) and Sprague-Dawley (SD) strains, and addressed the issue whether clozapine (atypical), compared to haloperidol (typical), effectively antagonizes MK801-induced PPI disruption.

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

In the rat, both the medial and lateral prefrontal cortices (PFC; mPFC and lPFC, respectively) have direct connections with limbic structures that are important in the expression of fear and anxiety. The present study investigated the behavioral effects of excitotoxic lesions of either the mPFC or the lPFC on conditioned and unconditioned fear paradigms. In both unconditioned fear paradigms (open field, elevated plus-maze), lesions of the mPFC decreased anxiety.

Sex differences in the acoustic startle response and prepulse inhibition in Wistar rats.

The prepulse inhibition paradigm (PPI) is based on the phenomenon that the acoustic startle response (ASR) to an acoustic stimulus is reduced when the stimulus is preceded by a weak prepulse. It has been shown that PPI is dramatically disrupted in patients with schizotypic disorders. Since PPI can be easily tested in animals as well as in humans it is a widely used model to investigate the neurobiological mechanisms underlying those disorders.

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

Latent inhibition (the retarded conditioning to a stimulus following its repeated non-reinforced pre-exposure) and prepulse inhibition (the reduction in the startle response to an intense acoustic stimulus when this stimulus is immediately preceded by a prepulse) reflect cognitive and sensorimotor gating processes, respectively, and are deficient in schizophrenic patients. The disruption of latent inhibition and prepulse inhibition in the rat is used as an animal model for the attentional deficits associated with schizophrenia. The present study tested the extent to which latent inhibition and prepulse inhibition, startle reaction and locomotor activity in the open field were affected by infusing the non-competitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine) into the dorsal hippocampus of Wistar rats.

Low-dose clozapine pretreatment partially prevents haloperidol-induced deficits in conditioned active avoidance.

The effectiveness of neuroleptics in disrupting conditioned active avoidance has led to the widespread use of this test as an index of antipsychotic efficacy, whereas the tendency for these drugs to induce catalepsy is believed to reflect their propensity to cause extrapyramidal motor side-effects. Although the typical neuroleptic haloperidol produces catalepsy as well as profound deficits in conditioned active avoidance, the atypical neuroleptic clozapine does not induce catalepsy and is less effective than haloperidol in disrupting active avoidance. Furthermore, clozapine pretreatment prevents haloperidol-induced catalepsy.

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

The effects of different schedules of cocaine administration on circadian activity patterns and locomotor sensitization were studied. Rats received intraperitoneal injections of either saline or 20 mg/kg cocaine at either 24- or 33-hr intervals for 8 cycles (development). After a 2-day withdrawal, they were given a cocaine challenge in a novel environment.

Long-term biobehavioral effects of maternal separation in the rat: consistent or confusing?

Over the last decades of research there has been increasing interest in endocrine and behavioral effects of postnatal environmental manipulations. A manipulation procedure that has been widely used to date is that of maternal separation. Many studies have demonstrated that, in the rat, a single or repeated separation of the pups from the mother leads to acute as well as long-term effects on endocrinology and behavior.

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

There is a well-described projection from the retrohippocampus (subiculum and entorhinal cortex) to the nucleus accumbens that is involved in the control of psychomotor behaviour, and is implicated in the aetiology of schizophrenia. Cortical abnormalities are widely reported in the brains of schizophrenic patients, but it is unclear whether they are the cause or consequence of those changes in subcortical systems that are treated with neuroleptic drugs. We have, therefore, conducted a series of microdialysis experiments in anaesthetized rats to determine whether infusion of the excitotoxin, N-methyl-D-aspartate, into the retrohippocampus increases mesolimbic dopamine release.

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

Rearing rats in isolation has been shown to be a relevant paradigm for studying early life stress and understanding the genesis of depression and related affective disorders. Recent studies from our laboratory point to the relevance of studying the social isolation syndrome as a function of home caging conditions. Accordingly, the present series of experiments assessed the contribution of each condition to the expression of the prepulse inhibition of the acoustic startle, food hoarding and spontaneous locomotor activity.

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

The latent inhibition (LI) phenomenon refers to the retardation in learning of an association between a stimulus and a consequence if that stimulus had been previously experienced without consequence. An earlier study demonstrated that the benzodiazepine receptor agonist chlordiazepoxide (CDP), when administered before the phase of preexposure to the to-be-conditioned stimulus, impaired animals' ability to develop LI. The present study was designed to investigate the effect of the anxiogenic drugs pentylenetetrazole (PTZ) and the benzodiazepine partial inverse agonist Ro15-4513 on LI.

Influence of promoter and WHV post-transcriptional regulatory element on AAV-mediated transgene expression in the rat brain.

Recombinant adeno-associated viruses (rAAVs) can transduce several tissues, including the brain. However, in brain the duration of gene expression in different areas is variable, which has been ascribed to viral (CMV) promoter silencing in some regions over time. We have compared expression of enhanced green fluorescent protein (EGFP) in the nigrostriatal pathway of rats mediated by rAAVs containing the CMV or platelet-derived growth factor-beta chain (PDGF-beta) promoter.

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

The activity of the striatum is regulated by glutamate and dopamine neurotransmission. Consequent to striatal dopamine depletion the corticostriatal excitatory input is increased, which in turn can raise intracellular calcium levels. We investigated changes in the neuronal expression of the calcium binding protein calretinin related to dopamine depletion and l-DOPA administration.

Strain differences in the isolation-induced effects on prepulse inhibition of the acoustic startle response and on locomotor activity.

The authors investigated the effects of isolation rearing on acoustic startle response, prepulse inhibition (PPI), its modification by apomorphine, and locomotor activity in 3 rat strains: Wistar (WS), Sprague-Dawley (SD), and Lister hooded (LH). SD and LH, but not WS, showed isolation-induced PPI deficits. In 2 consecutive PPI tests, only SD isolates showed significant PPI deficits.

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

Latent inhibition, the process whereby pre-exposure to a conditioned stimulus without consequence impairs subsequent learning of an association between the conditioned stimulus and an unconditioned stimulus, is reportedly disrupted in both amphetamine-treated rats and in acute schizophrenics. This has led to the suggestion that disruptions in latent inhibition model some of the cognitive impairments associated with hyperactive dopamine transmission as it is expressed in schizophrenic patients. Specifically, fluctuations in dopamine neurotransmission within the nucleus accumbens have been implicated in the mediation of latent inhibition; however, it has not been established whether these dopamine-mediated effects occur in the shell or core subregion of the nucleus.

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

Hypofunction of prefrontal cortical regions, such as dorsolateral and orbital regions, has been suggested to contribute to the symptomatology of schizophrenia. In the rat, the medial and the lateral prefrontal cortices are considered as homologs of the primate dorsolateral and orbital prefrontal cortices, respectively. The present study investigated in rats the effects of lesions of the medial and lateral prefrontal cortices on latent inhibition, prepulse inhibition and amphetamine-induced activity.

Isolation rearing-induced disruption of prepulse inhibition: further evidence for fragility of the response.

The present study investigated isolation-induced disruptions of prepulse inhibition (PPI), and effects on locomotor activity as a function of home caging condition (sawdust vs grid-floor) in the Wistar rat. Isolates reared in grid-floor cages did not show a disruption of PPI. However, when isolates were reared in sawdust cages, a PPI deficit was evident.

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

The present study sought to investigate the contributions of the dorsal prelimbic/anterior cingulate and ventral prelimbic/infralimbic cortices to the reverse microdialysis of amphetamine (1, 10, 100, 500, and 1000 microM) on dialysate acetylcholine, choline, norepinephrine, and serotonin levels. The results demonstrate that basal levels of acetylcholine, choline, and serotonin were homogeneous within subregions of the medial prefrontal cortex. In contrast, dialysate norepinephrine levels were significantly higher in the anterior cingulate cortex compared with the infralimbic cortex.

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

Hypotheses of the etiology of schizophrenia emphasize the important role of perinatal insults in predisposing individuals to the development of the disease, so that an animal model in which a discrete postnatal manipulation of the infant social environment yields schizophrenia-like behavior in adulthood would be valuable in terms of the study of the neural substrate and treatment of schizophrenia. Schizophrenics demonstrate a deficit in sensorimotor gating (prepulse inhibition), and a similar phenomenon has been described in adult rats following the administration of direct and indirect dopamine agonists. Recently it has been reported that a 24 h separation of rat pups from the mother results in a disruption of prepulse inhibition at adulthood.

Peripheral benzodiazepine receptors in cerebral cortex, but not in internal organs, are increased following inescapable stress and subsequent avoidance/escape shuttle-box testing.

Stress-induced alterations in peripheral benzodiazepine receptor (PBR) density have been reported in humans and in rats. However, the PBR response is highly specific, and its function remains largely unexplained. The aim of the present study was to investigate the relationship between behavior in the two-way active avoidance paradigm (2WAA) and post-test PBR densities in adrenal, testis, kidney, and cerebral cortex.

Dissociating context and space within the hippocampus: effects of complete, dorsal, and ventral excitotoxic hippocampal lesions on conditioned freezing and spatial learning.

Rats with complete excitotoxic hippocampal lesions or selective damage to the dorsal or ventral hippocampus were compared with controls on measures of contextually conditioned freezing in a signaled shock procedure and on a spatial water-maze task. Complete and ventral lesions produced equivalent, significant anterograde deficits in conditioned freezing relative to both dorsal lesions and controls. Complete hippocampal lesions impaired water-maze performance; in contrast, ventral lesions improved performance relative to the dorsal group, which was itself unexpectedly unimpaired relative to controls.

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

Postnatal environmental manipulations naturally occur on the background of prenatal experiences. In the laboratory rat, both pre- and postnatal environmental manipulations have been shown to alter adult behaviour. Additionally, it has been demonstrated that the consequences of postnatal manipulations can be altered by previous prenatal stress experience (PS).

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

Impaired ability to 'gate out' sensory and cognitive information is considered to be a central feature of schizophrenia and is manifested, among others, in disrupted prepulse inhibition (PPI) and latent inhibition (LI). The present study investigated in rats the effects of increasing or decreasing dopamine (DA) receptor activation within the medial prefrontal cortex (mPFC) by local administration of the indirect DA receptor agonist amphetamine (AMPH; 10.0 microg/side) or the DA antagonist cis-flupenthixol (FLU; 12.

Dissociative effects of apomorphine infusions into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition and amphetamine-induced locomotion.

Impaired ability to "gate out" sensory and cognitive information is considered to be a central feature of schizophrenia and is manifested, among others, in disrupted prepulse inhibition and latent inhibition. The present study investigated, in rats, the effects of increasing dopamine receptor activation within the medial prefrontal cortex by local administration of the dopamine receptor agonist apomorphine (9 microg/side) on prepulse inhibition and latent inhibition, as well as on spontaneous and amphetamine-induced activity. Apomorphine infusions decreased spontaneous locomotor activity and blocked amphetamine-induced increase in locomotor activity in the open field, which is in line with the suggestion that dopamine receptor activation in the medial prefrontal cortex inhibits mesolimbic dopamine activity.