Biomedical subjects

I Weiner

Publications and source records attributed to I Weiner.

At least 19 recordsLinked to original sources

PubMed1998

Electrolytic lesion of globus pallidus ameliorates the behavioral and neurodegenerative effects of quinolinic acid lesion of the striatum: a potential novel treatment in a rat model of Huntington's disease.

Bilateral electrolytic pallidal lesion ameliorated the deleterious effects of bilateral quinolinic acid (QA) lesion to the striatum on post-surgery weight, activity level, and performance in a water maze task, and reduced the extent of striatal damage. Given that the neurodegenerative and behavioral effects of QA striatal lesion are thought to mimic those seen in Huntington's disease, these results may point to a potential novel treatment for this disease.

Animals↗

PubMed1998

The effects of smoking on acoustic prepulse inhibition in healthy men and women.

Acoustic prepulse inhibition (PPI) refers to the reduction of the startle reflex to an intense stimulus if it is preceded by a weak stimulus. Nicotine and smoking have been reported to enhance PPI in rats and in healthy men, respectively. We studied the influence of smoking on PPI in healthy men and women, comparing non-smokers, deprived smokers, and smokers smoking during the test session after deprivation or after ad libitum smoking. Smoking during the session enhanced PPI, without affecting startle reaction or habituation over time. In addition, the effect of smoking on PPI was gender dependent. In men, ad libitum smoking enhanced PPI compared with non-smokers, while, in women, deprivation reduced PPI and smoking restored PPI to the level of non-smokers.

Acoustic Stimulation↗

PubMed1998

Differential effects of prenatal stress in two inbred strains of rats.

The long-term effects of prenatal stress (three times daily restraint stress during the last week of gestation) on the behavioral response to stress, as assessed by novelty-induced locomotion, performance in the forced swim test, and the acquisition of a two-way active avoidance, were investigated in two inbred strains of rats, Fischer 344 (F344/NHsd/Zur) and Lewis (LEW/SsNHsd/Zur). Additional measures included birth weights, pain threshold on the hot plate, and basal and stress-induced corticosterone secretion. In all of the behavioral paradigms strain differences were found: LEW rats showed poorer acquisition of avoidance conditioning, displayed higher levels of activity on the open plate, less immobility time in the forced swim test, and lower pain thresholds in the hot-plate test compared with F344 rats. LEW rats had higher birth weights after prenatal stress, whereas F344 rats were lighter. Following prenatal stress the pattern of behavioral effects obtained in LEW rats in stress-related tests could be interpreted as improved coping abilities with stress, i.e., improved acquisition of active avoidance, less immobility in the forced swim test, and reduced novelty-induced locomotion. Prenatal stress was much less effective in inducing long-term behavioral changes in F344 rats, yielding only one effect, namely, enhanced novelty-induced locomotion in female F344 rats. Pain thresholds were increased as a consequence of prenatal stress, irrespective of strain and gender. Basal and stress-induced corticosterone release differed in the two strains, with LEW rats showing less stress-induced corticosterone release. Prenatal stress did not, however, affect basal or stress-induced corticosterone release. The results suggest that prenatal stress exerts long-term effects on behavior, which depend on the genetic background.

Animals↗

PubMed1998

Rat strain differences in open-field behavior and the locomotor stimulating and rewarding effects of amphetamine.

Fischer 344 (F344) and Lewis (LEW) rats show considerable neuroanatomical and neurophysiological differences within the mesolimbic dopamine system. The aim of our experiments was to study the functional correlates of such differences by examining open-field behavior and the sensitivity towards the psychostimulant and rewarding effects of amphetamine in male and female, F344 and LEW rats. In addition, the consequences of short versus extended habituation to open-field testing on amphetamine locomotion in these two rat strains was assessed. LEW but not F344 rats irrespective of gender showed between-session habituation of open-field activity. Amphetamine-induced locomotion was higher in F344 compared to LEW rats and in females compared to male rats. In addition, extended habituation increased the locomotor effects of amphetamine. The rewarding effects of amphetamine as measured by the conditioned place preference test were more pronounced in F344 than in LEW rats. Our results suggest that the two rat strains differed in their behavioral response to mild stress and to amphetamine and that these differences may depend upon differences within the mesolimbic dopamine system.

Amphetamine↗

PubMed1998

Fimbria-fornix cut affects spontaneous activity, two-way avoidance and delayed non matching to sample, but not latent inhibition.

Latent inhibition (LI) consists of a decrement in conditioning to a stimulus as a result of its prior nonreinforced preexposure. Based on evidence pointing to the involvement of the hippocampus and the nucleus accumbens (NAC) in LI disruption, it has been proposed that LI depends on the integrity of the subicular input to the NAC. Since fibers originating in the subiculum and destined for the NAC run through the fimbria-fornix, we assessed the effects of fimbria-fornix lesion, made using a knife cut, on LI. In addition, we assessed the effects of the fimbria-fornix cut in three tests known to be sensitive to lesions to the hippocampal region, namely, spontaneous activity, two-way active avoidance and delayed-non-matching-to-sample. In accord with previously documented effects of lesions to the hippocampus and related structures, the fimbria-fornix cut increased spontaneous activity (Experiment 1), facilitated the acquisition of two-way active avoidance (Experiment 3), and produced a delay-dependent deficit in the delayed-non-match-to-sample task (Experiment 4), demonstrating that it disrupted hippocampal functioning. In contrast, LI remained unaffected by the fimbria-fornix cut (Experiment 2), indicating that disruption of subicular input to the NAC is not responsible for the attenuation of LI following non-selective hippocampal lesions. The implications of these results for the neural circuitry of LI are discussed.

Adaptation, Psychological↗

PubMed1998

The effects of excitotoxic lesion of the medial prefrontal cortex on latent inhibition, prepulse inhibition, food hoarding, elevated plus maze, active avoidance and locomotor activity in the rat.

Latent inhibition is a measure of retarded conditioning to a previously presented nonreinforced stimulus that is impaired in schizophrenic patients and in rats treated with amphetamine. In terms of neural substrates, latent inhibition depends on the integrity of the nucleus accumbens and the inputs to this structure from the hippocampal formation and adjacent cortical areas. Since another major source of input to the nucleus accumbens is the medial prefrontal cortex, and there are numerous demonstrations that manipulations of this region can modify ventral striatal dopamine, we investigated the effects of N-methyl-D-aspartate lesion to the medial prefrontal cortex on latent inhibition, assessed in an off-baseline conditioned emotional response procedure in rats licking for water. In addition, the effects of the medial prefrontal cortex lesion were assessed on a battery of tasks potentially sensitive to medial prefrontal cortex damage, including spontaneous and amphetamine-induced activity, elevated plus maze exploration, food hoarding, prepulse inhibition, and active avoidance. The lesion decreased hoarding behaviour and increased spontaneous exploratory activity in the open field, while exerting only mild effects on amphetamine-induced activity. Prepulse inhibition, exploration of the elevated plus maze, and the acquisition of two-way active avoidance were unaffected by the lesion. Likewise, latent inhibition was left intact following the lesion, suggesting that neither the destruction of the intrinsic cells of the medial prefrontal cortex nor any potential lesion-induced changes in subcortical dopamine, affect latent inhibition.

Acoustic Stimulation↗

PubMed1998

Haloperidol-induced potentiation of latent inhibition: interaction with parameters of conditioning.

If a stimulus (e.g. tone or light) is repeatedly pre-exposed without consequences, it subsequently shows retarded conditioning when paired with a reinforcer (e.g. footshock) compared with a non-pre-exposed stimulus. This is latent inhibition (LI). Haloperidol-treated animals show potentiated LI, and it has been suggested that this is due to retarded switching to respond according to the stimulus-reinforcer contingency. Recently, it has been argued that the slowed control of behaviour by the stimulus-reinforcement contingency is due to a haloperidol-induced decrease in the impact, or salience, of the reinforcer, and thus should be antagonized by increasing the impact of reinforcement. Two experiments tested this prediction. In both, LI was assessed using an off-baseline conditioned emotional response procedure in rats licking for water. In Experiment 1, rats were given 10 light pre-exposures and conditioned with two footshocks of either a low (0.5 mA) or a high (1 mA) intensity. In Experiment 2, rats were given 30 pre-exposures and conditioned with either two or five footshocks of 1 mA. In Experiment 1, no-drug controls did not show LI at both shock intensities. Haloperidol (0.1 mg/kg) was ineffective in potentiating LI at low-intensity shock, but produced LI when shock level was increased. In Experiment 2, no-drug controls showed LI with two but not five conditioning trials. Haloperidol was ineffective in potentiating LI with two conditioning trials, but produced LI with five conditioning trials. Although the effect of haloperidol on LI could thus be modified by manipulating shock intensity or the number of conditioning trials, the direction of such modification indicates that the potentiating effect of haloperidol on LI is not in general antagonized by increasing the impact of reinforcement.

Animals↗

PubMed1997

Effects of electrolytic lesions of the medial prefrontal cortex or its subfields on 4-arm baited, 8-arm radial maze, two-way active avoidance and conditioned fear tasks in the rat.

The present study tested the effects of electrolytic lesions in two mPFC subregions, the dorsal anterior cingulate area (dACA) and prelimbic cortex, as well as the effects of a larger medial prefrontal cortex (mPFC) lesion which included both subregions, on 4-arm baited, 4-arm unbaited, 8-arm radial maze task and its reversal (Experiments 1 and 4), two-way active avoidance (Experiments 2 and 5) and conditioned emotional response (Experiments 3 and 6). Rats with large or small lesions of the mPFC learned the location of the 4 baited arms in the training and reversal stages of the radial maze task similarly to sham rats, indicating that these lesions did not affect animals' capacity to process and remember spatial information. dACA and mPFC lesions produced a transient deficit in the acquisition of the radial maze task, suggestive of an involvement of these regions in mnemonic processes. However, in view of the normal performance of these groups by the end of training and during reversal, this deficit is better interpreted as stemming from a difficulty to learn the memory-based strategy used to solve the task. Only mPFC lesion led to better avoidance performance at the beginning of training and tended to increase response during the presentation of a stimulus previously paired with shock, compared to sham rats. Both effects can be taken as an indication of reduced emotionality following mPFC lesion. The results are discussed in relation to known behavioral functions of the mPFC and the suggested functional specialization within this region.

Animals↗

PubMed1997

Neonatal nonhandling and in utero prenatal stress reduce the density of NADPH-diaphorase-reactive neurons in the fascia dentata and Ammon's horn of rats.

The density of nitric oxide (NO)-producing neurons in the fascia dentata and Ammon's horn was assessed in 6-month-old male rats using NADPH-diaphorase (NADPH-d) histochemistry. Two separate experiments investigated whether (1) the complete absence of neonatal handling or (2) the administration of periodic prenatal stress could affect the expression and distribution of NADPH-d reactivity in the hippocampus, when compared with rats raised in normal standard laboratory conditions. Experiment 1 demonstrated that adult rats that received no handling during neonatal development (from birth to postnatal day 22) showed a very substantial reduction in NADPH-d-positive neurons per unit area throughout the entire hippocampus when compared with rats that received regular daily handling in this period. Quantitative analysis further revealed that this effect was significantly more pronounced in Ammon's horn than in the fascia dentata, and within Ammon's horn the dorsal region was selectively more affected. Experiment 2 showed that prenatal stress, which involved the administration of daily restraint stress to pregnant dams throughout the gestation period, also led to a reduction in NADPH-d reactivity in the hippocampus of the offspring of these dam when they reached adulthood. The present results suggest that behavioral manipulations in the early neonatal or prenatal period can significantly alter the neurodevelopment of the hippocampal NO system and these changes might be related to some of the behavioral abnormalities that emerge later in adulthood.

Animals↗

PubMed1997

Amphetamine-induced disruption of latent inhibition is not reinforcer-mediated.

Latent inhibition (LI) refers to retarded conditioning to a stimulus that had been repeatedly preexposed without consequences, as compared with a nonpreexposed stimulus. Amphetamine disrupts LI, and this effect was suggested to result from enhanced switching to respond according to the stimulus-reinforcer contingency. Recently, it has been argued that amphetamine disrupts LI by increasing the impact of the reinforcer. This implies that amphetamine should produce stronger conditioning in the nonpreexposed group and that its influence on LI can be modified only by changing reinforcer parameters. We report two studies, using an off-baseline conditioned emotional response procedure in rats licking for water, that question both predictions. In the first study, a meta-analysis based on 23 replications of the effect of amphetamine on LI, using tone as the preexposed stimulus, showed that LI is significantly attenuated due to drug-induced increased suppression in the preexposed groups only. The second study included two experiments, each using two shock intensities but different preexposed stimuli. Amphetamine disrupted LI at both shock intensities when the stimulus was a steady light, but this effect disappeared when the stimulus was three flashing lights. Thus, the effect of amphetamine could not be modified by manipulating shock intensity, but was modifiable by manipulating the nature of the preexposed stimulus. The results are inconsistent with the hypothesis that amphetamine-induced disruption of LI is solely mediated by drug-induced changes in the effects of reinforcers.

Animals↗

PubMed1997

The connections of the primate subthalamic nucleus: indirect pathways and the open-interconnected scheme of basal ganglia-thalamocortical circuitry.

The current view of basal ganglia organization holds that functionally corresponding subregions of the frontal cortex, basal ganglia and thalamus form several parallel segregated basal ganglia-thalamocortical circuits. In addition, this view states that striatal output reaches the basal ganglia output nuclei (the substantia nigra pars reticulata (SNR) and the internal segment of the globus pallidus (GPi)) via a 'direct' pathway, and via an 'indirect pathway' which traverses the external segment of the globus pallidus (GPe) and the subthalamic nucleus (STN). However, the topographical relationships of GPe and STN, and their topographical relationships with the basal ganglia-thalamocortical circuits are still unclear. The present work reviewed primate data on the topographical organization of STN afferents from GPe, and STN efferents to the pallidum, striatum and SNR, and examined these data with respect to a tripartite (motor, associative and limbic) functional subdivision of the striatum and pallidum. This examination indicated the following. (1) On the basis of its efferent connections, the STN may be divided into a motor and an associative territories, as well as a smaller limbic territory, each projecting to corresponding areas in the pallidum and striatum. (2) Efferents from GPe are in a position to contact subthalamic cells projecting to GPi/SNR, thus providing anatomical support for the existence of indirect pathways. (3) Moreover, given the tripartite division of the striatum, pallidum, and STN, the available data indicate the existence of indirect pathways connecting functionally corresponding subregions of the striatum, pallidum, and STN, as well as indirect pathways connecting functionally non-corresponding subregions. On the basis of the above we suggested that there may be two types of indirect pathways, one which terminates in the same subregion in GPi/SNR as the direct pathway arising from the same striatal subregion, and another which terminates in a different GPi/SNR subregion than the direct pathway arising from the same striatal subregion. We termed the former a 'closed indirect pathway' and the latter an 'open indirect pathway'. The application of these concepts to the surveyed data suggested the existence of three closed indirect pathways, each connecting the corresponding functional (motor, associative, and limbic) regions of the striatum, pallidum, STN, and SNR, as well as of two open indirect pathways, one connecting the associative striatum to the motor subregions of the basal ganglia, and the other connecting the associative striatum to the limbic subregions of the basal ganglia. While the organization of the closed indirect pathways fits the closed segregated arrangement of basal ganglia-thalamocortical circuitry, the organization of the open indirect pathways fits the recently suggested open interconnected scheme of basal ganglia thalamocortical circuitry. The clinical implications of this scheme for Huntington's disease are discussed.

Animals↗

PubMed1997

Amphetamine-induced disruption and haloperidol-induced potentiation of latent inhibition depend on the nature of the stimulus.

If a stimulus (e.g. light) is repeatedly preexposed without consequences, it subsequently develops a weaker association with a reinforcer (e.g. foot shock) than does a non-preexposed stimulus. This retarded conditioning to the preexposed as compared to the non-preexposed stimulus, is latent inhibition (LI). It is well documented that LI is disrupted by low doses of amphetamine and potentiated by neuroleptic drugs, and there is evidence that the action of these agents on LI can be modified by changes in the parameters of preexposure or conditioning. The present experiments tested whether the effects of DA agents on LI are influenced by the nature of the stimulus. In two experiments, LI was assessed using an off-baseline conditioned emotional response (CER) procedure in rats licking for water, consisting of three stages: preexposure, in which the stimulus (a light) to be conditioned, was repeatedly presented without being followed by reinforcement; conditioning, in which the preexposed stimulus was paired with reinforcement (a foot-shock); and test, in which LI was indexed by animals' degree of suppression of licking during stimulus presentation. In both experiments, different groups of animals were preexposed and conditioned with four different preexposed visual stimuli: three steady side-lights, three flashing side-lights, one flashing side-light, and a flashing houselight. Experiment 1 used 40 stimulus preexposures and tested the effects of 1 mg/kg D-amphetamine, whereas experiment 2 used 10 preexposures and tested the effects of 0.1 mg/kg haloperidol. The results showed that of the four stimuli used, both drugs were effective with only one and the same stimulus, namely, flashing houselight. This demonstrates that the disruptive effect of amphetamine and the potentiating effect of haloperidol on LI, are modifiable by manipulating the nature of the preexposed stimulus.

Animals↗

PubMed1997

The switching model of latent inhibition: an update of neural substrates.

Organisms exposed to a stimulus which has no significant consequences, show subsequently latent inhibition (LI), namely, retarded conditioning to this stimulus. LI is considered to index the capacity to ignore irrelevant stimuli and its disruption has recently received increasing interest as an animal model of cognitive deficits in schizophrenia. Initial studies indicated that LI is disrupted by systemic or intra-accumbens injections of amphetamine and hippocampal lesions, and potentiated by systemic administration of neuroleptics. On the basis of these findings, the switching model of LI proposed that LI depends on the subicular input to the nucleus accumbens (NAC). Subsequent studies supported and refined this proposition. Lesion studies show that LI is indeed disrupted by severing the subicular input to the NAC, and further implicate the entorhinal/ventral subicular portion of this pathway projecting to the shell subterritory of the NAC. There is a functional dissociation between the shell and core subterritories of the NAC, with lesions of the former but not of the latter disrupting LI. This suggests that the shell is necessary for the expression and the core for the disruption of LI. The involvement of the NAC has been also demonstrated by findings that LI is disrupted by intra-accumbens injection of amphetamine and potentiated by DA depletion or blockade in this structure. Disruption and potentiation of LI by systemic administration of amphetamine and neuroleptics, respectively, have been firmly established, and in addition, have been shown to be sensitive to parametric manipulations of the LI procedure. LI is unaffected by lesions and DA manipulations of medial prefrontal cortex and lesions of basolateral amygdala. The implications of these findings for LI as an animal model of schizophrenia are discussed.

Animals↗

PubMed1997

Electrolytic lesions of the medial prefrontal cortex in rats disrupt performance on an analog of the Wisconsin Card Sorting Test, but do not disrupt latent inhibition: implications for animal models of schizophrenia.

The effects of electrolytic lesions of the medial prefrontal cortex (mPFC) or its subregions were investigated on two cognitive tests that may have relevance to the behavioral impairments of patients with schizophrenia. One task consisted of a delayed non-match-to-sample and reversal of the non-match-to-sample rule, in a Skinner box. The reversal component simulated the essential feature of rule shifting of the Wisconsin Card Sorting Test (WCST), which is a commonly used test for assessing 'frontal-like' deficits in schizophrenia. The second was latent inhibition, in which repeated pre-exposure to a stimulus without consequence retards subsequent associations with that stimulus. Latent inhibition is impaired in acute schizophrenic patients, and its disruption in the rat has been suggested to constitute an animal model of schizophrenia. Expts. 1 and 2 tested the effects of lesions of the dorsal anterior cingulate cortex (dACA) and mPFC, respectively, on the WCST analog. Expt. 3 tested the effects of lesions of the dACA or infralimbic cortex, and Expt. 4 tested the effects of mPFC lesion, on latent inhibition. Lesions of mPFC subregions had no effect. mPFC lesion produced transient deficits in the performance of the DNMS task and impaired the reversal from the non-match-to-sample to the match-to-sample rule, but left the latent inhibition effect intact. Possible relevance of this behavioral profile of mPFC lesion to the 'frontal syndrome' is discussed.

Animals↗

PubMed1997

Haloperidol- and clozapine-induced enhancement of latent inhibition with extended conditioning: implications for the mechanism of action of neuroleptic drugs.

Latent inhibition (LI) refers to retarded conditioning to a stimulus as a consequence of its nonreinforced preexposure. LI is impaired in acute schizophrenic patients and in rats treated with amphetamine. Neuroleptic drugs enhance LI, and this effect is selective and specific for this class of drugs. The present experiments tested the proposition that neuroleptic-induced enhancement of LI stems from decreased capacity of stimulus-preexposed animals to switch responding according to the new stimulus-reinforcement contingency in the conditioning stage. LI was assessed using an off-baseline conditioned emotional response (CER) procedure in rats licking for water, consisting of three stages: preexposure to the-to-be conditioned stimulus, tone; conditioning, in which the preexposed stimulus was paired with a foot-shock; and test, in which LI was indexed by animals' degree of suppression of licking during tone presentation. Whereas in previous studies that demonstrated LI enhancement by neuroleptics, preexposure consisted of 10 to 40 tones, and conditioning included two tone-shock pairings, the present experiments used 40 tone preexposures, followed by an extended conditioning stage with five tone-shock pairings. It was expected that under these conditions no LI effect would be evident in untreated animals, but that animals treated with a neuroleptic drug, either during the entire LI procedure or only in conditioning, would show LI. Experiments 1 and 2 showed that LI was obtained in rats treated with haloperidol (0.1 mg/kg in experiment 1, 0.03 and 0.2 mg/kg in experiment 2) but not in the untreated controls. Experiment 3 showed that the same outcome was obtained when haloperidol (0.1 mg/kg) administration was confined to the conditioning stage. Experiment 4 showed that clozapine (5 mg/kg)-treated animals showed LI when the drug was confined to conditioning, but not to the preexposure stage. The implications of these results for the mechanism of action of neuroleptic drugs are discussed.

Acoustic Stimulation↗

PubMed1997

The effects of electrolytic lesion to the shell subterritory of the nucleus accumbens on delayed non-matching-to-sample and four-arm baited eight-arm radial-maze tasks.

The effects of bilateral electrolytic lesions of the "shell" subterritory of the nucleus accumbens in the rat were examined on 2 tasks known to be sensitive to hippocampal damage. Experiment 1 tested the effects of shell lesion on delayed non-matching-to-sample (DNMS) task in a T-maze. The maze was rotated 180 degrees after the end of acquisition. Experiment 2 used a 4-arm baited, 4-arm unbaited, 8-arm radial-maze task and its reversal. Shell lesion led to impaired acquisition of DNMS in a T-maze and of 4-arm baited, 4-arm unbaited, 8-arm radial maze tasks, suggestive of mnemonic deficits. Following analysis of animals' choice pattern in both tasks, the deficit was interpreted as being largely due to an extensive use of response strategy. The results suggest that the inappropriate use of response strategy by shell animals was a result of their inability to switch from initial response strategy to a later, more appropriate, memory-dependent strategy.

Animals↗

PubMed1997

Amphetamine-induced disruption of latent inhibition depends on the nature of the stimulus.

It is well documented that latent inhibition (LI), i.e. slower conditioning to a stimulus that had been repeatedly pre-exposed without consequences, compared to a non-pre-exposed stimulus, is prevented by amphetamine. Recently, we found that the effects of amphetamine on LI, as assessed in an off-baseline conditioned emotional response (CER) procedure, depend on the nature of the pre-exposed stimulus, irrespective of reinforcer intensity. Because these results contrast with a recent finding that a reduction in reinforcer intensity reversed amphetamine-induced attenuation of LI in an on-baseline CER procedure, the present study investigated the effects of amphetamine on LI as a function of the nature of the pre-exposed stimuli and shock intensity, using an on-baseline CER procedure. The effects of amphetamine on post-shock suppression of drinking as well as on activity, were monitored throughout the stages of the CER procedure. Experiment 1 used a 5 s steady light as the pre-exposed and conditioned stimulus, and two shock intensities in conditioning, and Experiment 2 used a 10 s flashing light and two shock intensities. Amphetamine disrupted LI with a steady light at both low and high shock intensities, but failed to disrupt LI with a flashing light at both shock intensities. In addition, the drug disrupted LI in Experiment 3, which increased the duration of the steady light to 10 s and used only low shock intensity, but failed to affect LI in Experiment 4 which used the flashing light on the background of darkness or of light, and only high shock intensity. The effects of amphetamine on LI were not related to its effects on behavioural suppression after footshock, or on activity.

Amphetamine↗

PubMed1996

The latent inhibition model of schizophrenia: further validation using the atypical neuroleptic, clozapine.

Latent inhibition (LI) refers to retarded conditioning to a stimulus that has been repeatedly presented without reinforcement. LI is impaired in schizophrenia patients and in rats treated with amphetamine. Neuroleptic drugs produce two effects in this test paradigm: antagonism of amphetamine-induced disruption of LI, and enhancement of LI when administered on their own. The present experiments tested the effects of the atypical neuroleptic, clozapine, on LI. The experiments used a conditioned emotional response procedure in rats licking for water, consisting of three stages: preexposure, in which the to-be-conditioned stimulus (tone) was repeatedly presented without reinforcement; conditioning, in which the preexposed stimulus was paired with reinforcement (foot shock); and test, in which LI was indexed by animals' degree of suppression of licking during tone presentation. In experiments 1 and 2, the effects of 5.0 and 10.0 mg/kg clozapine on LI were assessed following 20 or 10 tone preexposures, respectively. Experiments 3 and 4 used 40 preexposures and investigated antagonism of amphetamine-induced disruption of LI by 5.0 and 10.0 mg/kg clozapine, respectively. The results demonstrated that clozapine possesses a neuroleptic profile in the LI model, namely, it facilitates the development of LI and antagonizes amphetamine-induced disruption of LI.

Animals↗