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I Weiner

Publications and source records attributed to I Weiner.

At least 55 records · Page 3Linked to original sources
PubMed1995

Basolateral amygdala lesions do not disrupt latent inhibition.

Latent inhibition (LI) is a measure of retarded conditioning to a previously presented non-reinforced stimulus that is impaired in schizophrenic patients and in rats treated with amphetamine, and is restored in both by neuroleptic drugs. In terms of neural substrates, LI depends on the integrity of the nucleus accumbens (NAC) and the inputs to this structure from the hippocampal formation and adjacent cortical areas. The present experiments investigated the effects of electrolytic lesions to the basolateral amygdala (BLA), which is another major source of input to the NAC, on the LI effect. LI was assessed in a conditioned emotional response (CER) procedure in rats licking for water, consisting of three stages: pre-exposure, in which the to-be-conditioned stimulus (a tone) was repeatedly presented without being followed by reinforcement; conditioning, in which the pre-exposed stimulus was paired with reinforcement (a foot shock); and test, in which LI was indexed by the animal's degree of suppression of licking during tone presentation. In Expt. 1, which used a lesion at a more posterior location, no effect on either LI or CER conditioning was seen. In Expt. 2, lesion at a more anterior location reduced the magnitude of CER conditioning in both the pre-exposed and the non-pre-exposed animals, but left the LI effect intact. The latter lesion did not affect spontaneous and amphetamine-induced activity (Expt. 3). These results suggest that the development of LI is not dependent on the amygdalar input to the NAC, but that the input from the anterior aspects of BLA to the NAC is involved in the establishment of stimulus-reinforcement associations.

Acoustic Stimulation↗
PubMed1994

Antagonism of amphetamine-induced disruption of latent inhibition in rats by haloperidol and ondansetron: implications for a possible antipsychotic action of ondansetron.

Latent inhibition (LI) is a behavioural phenomenon whereby preexposure to a stimulus without reinforcement interferes with the formation of subsequent associations to that stimulus. Using preexposure to a tone stimulus which subsequently serves as a conditioned stimulus for suppression of licking, we have confirmed that LI is disrupted by a low dose of amphetamine. Haloperidol was able to prevent this effect of amphetamine. Ondansetron, a selective and potent 5HT3 receptor antagonist, was also shown to be effective at blocking the amphetamine-induced disruption of LI at a dose of 0.01 mg/kg, but not at 0.1 mg/kg. In addition, it was demonstrated that ondansetron could enhance LI; using only ten preexposures, no LI was obtained in the saline group, but was apparent in animals given ondansetron, an effect which has been previously shown with haloperidol. Haloperidol, at the higher dose used, reduced suppression of licking, however, ondansetron at the effective dose had no such effect. It is concluded that ondansetron is able to attenuate increases in dopamine activity, produced pharmacologically with amphetamine without affecting baseline dopamine activity. The implications of these findings for a possible antipsychotic action of ondansetron are discussed.

Acoustic Stimulation↗
PubMed1994

The organization of the basal ganglia-thalamocortical circuits: open interconnected rather than closed segregated.

Anatomical findings in primates and rodents have led to a description of several parallel segregated basal ganglia-thalamocortical circuits leading from a distinct frontocortical area, via separate regions in the basal ganglia and the thalamus, back to the frontocortical area from which the circuit originates. One of the questions raised by the concept of parallelism is whether and how the different circuits interact. The present Commentary proposes that interaction is inherent in the neural architecture of the basal ganglia-thalamocortical circuits. This proposal is based on the re-examination of the data on the topographical organization of the frontocortical-basal ganglia connections which indicates that each circuit-engaged striatal region sends divergent projections to parts of both substantia nigra pars reticulata and the internal segment of the globus pallidus (each ventral striatal region sends divergent projections to parts of ventral pallidum, substantia nigra pars reticulata and globus pallidus), and this segregation is maintained at subsequent thalamic and frontocortical levels. This results in an asymmetry in the frontal cortex-basal ganglia relationships, so that while each frontocortical subfield innervates one striatal region, each striatal region influences the basal ganglia output to two frontocortical subfields. Because of this asymmetry, at least one of the frontocortical targets of a given circuit-engaged striatal region is not the source of its frontocortical input. Since this organization is inconsistent with an arrangement in closed segregated circuits we introduce the concept of a "split circuit". A split circuit emanates from one frontocortical area, but terminates in two frontocortical areas. Thus, a split circuit contains at least one "open" striato-fronto-cortical pathway, that leads from a circuit-engaged striatal region to a frontocortical area which is a source of a different circuit. In this manner split circuits are interconnected via their open pathways. The second striato-fronto-cortical pathway of a split circuit can be another open pathway, or it can re-enter the frontocortical area of origin, forming a closed circuit. On the basis of the available anatomical data we tentatively identified a motor, an associative, and a limbic split circuit, each containing a closed circuit and an open pathway. The motor split circuit contains a closed motor circuit that re-enters the motor and premotor cortical areas and an open motor pathway that terminates in the associative prefrontal cortex. The associative split circuit contains a closed associative circuit that re-enters the associative prefrontal cortex and an open associative pathway that terminates in the premotor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

From an animal model of an attentional deficit towards new insights into the pathophysiology of schizophrenia.

The paper presents an animal model of schizophrenic-like attentional deficit, consisting of an inability to ignore irrelevant stimuli. It is based on the paradigm of latent inhibition (LI), in which animals learn to ignore repeatedly presented stimuli not followed by meaningful consequences. In a series of experiments it was demonstrated that the capacity to ignore irrelevant stimuli is lost in rats treated with systemic or intra-accumbens injections of amphetamine, in normal volunteers given amphetamine, in high "psychosis-prone" persons, in acute schizophrenic patients and in untreated male adult rats that were raised until weaning under conditions of extremely restricted stimulation. In addition, LI is lost following the disruption of the hippocampal input to the nucleus accumbens. In all of the above conditions tested for antagonism by anti-psychotic drugs a loss of LI is reversed. On the basis of these results we propose an animal model which accommodates a neurodevelopmental dysfunction, hippocampal pathology, mesolimbic DA overactivity, vulnerability to stress, and gender differences, all of which have been postulated as factors in the pathophysiology of schizophrenia.

Animals↗
PubMed1992

Phencyclidine does not disrupt latent inhibition in rats: implications for animal models of schizophrenia.

Latent inhibition (LI) is a behavioral paradigm in which prior exposure to a stimulus not followed by reinforcement retards subsequent conditioning to that stimulus when it is paired with reinforcement. The development of LI reflects a process of learning to ignore, or tune out, irrelevant stimuli. Three experiments investigated the effects of phencyclidine (PCP) on LI. The investigation was carried out using a conditioned emotional response (CER) procedure 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 shock; and test, where LI was indexed by animals' suppression of licking during tone presentation. The three stages were conducted 24 h apart. In Experiment 1, 1 mg/kg PCP was administered either in the preexposure or in the conditioning stage or in both. Experiment 2 used 5 mg/kg PCP in the same procedure. In Experiment 3, 5 mg/kg PCP was administered throughout the LI procedure, including the test stage. In all three experiments, PCP did not affect LI. The implications of these findings for the development of animal models of schizophrenia are discussed.

Amphetamine↗
PubMed1992

Amphetamine and the multitrial partial reinforcement extinction effect (PREE) in an operant chamber: procedural modifications that lead to an attenuation of the PREE.

The partial reinforcement extinction effect (PREE) consists of the fact that animals receiving partial reinforcement (PRF) exhibit higher resistance to extinction than animals receiving continuous reinforcement (CRF). In previous studies, we found that amphetamine (AMPH) did not affect resistance to extinction of PRF animals trained with a multitrial procedure, but abolished resistance to extinction of PRF animals trained with a 1 trial/day procedure. Based on theoretical distinctions regarding the processes underlying the development of increased resistance to extinction at short and long intertrial intervals, we suggested that AMPH disrupts the formation of a context-mediated association between stimuli associated with nonreinforcement and subsequent reinforcement. To examine further this possibility, we designed conditions in a multitrial PRF procedure that do not allow a direct association between stimuli associated with nonreinforcement and reinforcement, and thus promote a context-mediated association between them. Two experiments were conducted in an operant chamber. In experiment 1, instead of the conventional 50% schedule of reinforcement throughout PRF training, days of 33% schedule of reinforcement were interspersed with days of continuous reinforcement; in experiment 2, a block (5 days) of 50% PRF schedule was alternated with a block (5 days) of CRF training, given either prior to or following PRF. In experiment 1, interspersing days of CRF training with days of 33% reinforcement schedule led to an attenuation of the PREE in AMPH-treated animals. In experiment 2, control animals that received CRF training either prior to or following PRF training exhibited a PREE similar to animals trained on PRF alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1992

A neuroleptic-like effect of ceronapril on latent inhibition.

Three experiments that used a latent inhibition procedure to investigate the effects of ceronapril on attentional processes in the rat are reported. Latent inhibition is a behavioural paradigm in which prior exposure to a stimulus with no significant consequences retards subsequent conditioning to that stimulus when it is paired with reinforcement. Latent inhibition reflects a process of learning to ignore, or tune out, irrelevant stimuli, and has been suggested as an animal model of the attentional processes disrupted in the acute phase of schizophrenia. In animals, latent inhibition is disrupted by the administration of low doses of amphetamine and enhanced by the administration of neuroleptics. Ceronapril is an angiotensin converting enzyme inhibitor that has been shown to retard the breakdown of central cholecystokinin. It has been proposed that elevation of cholecystokinin levels in the brain may possess neuroleptic-like properties. We assessed this possibility by determining the effects of ceronapril on latent inhibition using a conditioned emotional response procedure, consisting of three stages: pre-exposure, in which the to-be-conditioned stimulus, a tone, was repeatedly presented without reinforcement; conditioning, in which the pre-exposed stimulus was paired with shock; and test, where latent inhibition was indexed by animals' suppression of licking during tone presentation. In Experiment 1, 20 tone pre-exposures were given, and conditioning consisted of five tone-shock pairings; we assessed the effects of 0.005 mg/kg, 0.05 mg/kg and 0.5 mg/kg ceronapril, compared with vehicle injections. In Experiment 2, five tone pre-exposures were given, and conditioning consisted of two tone-shock pairings: we assessed the effects of 0.05 mg/kg ceronapril, compared with vehicle injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1991

The latent inhibition model of schizophrenic attention disorder. Haloperidol and sulpiride enhance rats' ability to ignore irrelevant stimuli.

Latent inhibition (LI) is a behavioral paradigm in which prior exposure to a stimulus not followed by reinforcement retards subsequent conditioning to that stimulus when it is paired with reinforcement. The development of LI reflects a process of learning to ignore, or tune out, irrelevant stimuli. Two experiments investigated the effects of haloperidol (0.02, 0.1, and 0.5 mg/kg) and sulpiride (100 mg/kg) administration on LI. The investigation was carried out using a conditioned emotional response (CER) procedure consisting of three stages: (1) preexposure, in which the to-be-conditioned stimulus, tone, was repeatedly presented without reinforcement; (2) conditioning, in which the preexposed stimulus was paired with shock; and (3) test, where LI was indexed by animals' suppression of licking during tone presentation. The three stages were conducted 24 hr apart. In the preexposure stage, only ten nonreinforced stimulus preexposures were given, a procedure known to be insufficient to yield LI in normal animals. In both experiments, LI was indeed absent in the placebo animals. In marked contrast, animals treated with haloperidol (experiment 1) as well as with sulpiride (experiment 2) exhibited LI. These results demonstrate that both typical and atypical neuroleptics enhance animals' capacity to ignore irrelevant stimuli. The implications of this finding for an animal model of schizophrenia and for a novel screening test for antipsychotic drugs are discussed.

Animals↗
PubMed1991

Effects of haloperidol on the multitrial partial reinforcement extinction effect (PREE): evidence for neuroleptic drug action on nonreinforcement but not on reinforcement.

Two experiments investigated the effects of haloperidol (0.1 mg/kg) on the partial reinforcement extinction effect (PREE). In experiment 1 two groups of rats were trained to run in a straight alley using six trials/day with an intertrial interval (ITI) of 5-8 min. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasi-random 50% schedule. All animals were then tested in extinction. Haloperidol was administered in a 2 x 2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. In experiment 2 two groups of rats were trained to press a lever in an operant chamber using a discrete trial procedure of ten trials/day with an ITI of 60 s. The CRF group was rewarded on each trial and the PRF group was rewarded on a quasi-random 50% schedule. Haloperidol was administered for 22 days prior to the start of the PREE procedure as well as throughout acquisition and extinction. The PREE, i.e., increased resistance to extinction of PRF as compared to CRF animals, was obtained in both experiments in all drug conditions. In both experiments haloperidol increased the rate of extinction. Experiment 1 revealed that this effect was entirely due to the administration of the drug in extinction, independently of the drug condition in acquisition. In contrast to previous results in a one trial/day procedure, the administration of haloperidol to CRF animals did not increase resistance to extinction, failing to support the notion that neuroleptics attenuate the rewarding properties of reinforcement.

Animals↗
PubMed1991

Latent inhibition is unaffected by direct dopamine agonists.

Latent inhibition (LI) refers to the finding that nonreinforced preexposure to a stimulus retards subsequent conditioning to that stimulus when it is paired with reinforcement. The development of LI reflects a process of learning not to attend, or ignore, irrelevant stimuli. Previous experiments showed that LI was disrupted by low but not high doses of amphetamine, and facilitated by neuroleptic drugs. The present experiments sought to investigate the role of dopamine D1 and D2 receptors in LI disruption. Experiments 1 and 2 showed that the selective D1 agonist, SKF-38393 (1, 5, 10 mg/kg) and the selective D2 agonist, quinpirole (0.1, 0.3, 1.0 mg/kg), did not affect LI. Experiment 3 showed that both low (0.3 mg/kg) and high (1.5 mg/kg) doses of the mixed D1-D2 agonist, apomorphine, failed to affect L1. These results show that L1 is not disrupted by direct stimulation of DA receptors and suggest that the differential effect exerted on this phenomenon by apomorphine (and possibly SKF-38393 and quinpirole) and amphetamine is related to the direct versus the indirect agonist action of these drugs. In addition, apomorphine at the dose of 0.03 mg/kg, which is believed to activate preferentially DA autoreceptors, did not produce neuroleptic-like facilitation of LI. The implications of the results of the involvement of DA mechanisms in L1 are discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

The effects of pre- and postweaning rearing conditions on latent inhibition and partial reinforcement extinction effect in male rats.

Male rats were either handled daily or left undisturbed (nonhandled) during the first 21 days of life. At weaning (Day 22) animals in each early treatment condition were assigned to two housing conditions, isolated or grouped, creating four early/late treatment conditions: Handled-Grouped (HG), Handled-Isolated (HI), Nonhandled-Grouped (NHG), and Nonhandled-Isolated (NHI). At maturity, all animals were tested in the latent inhibition (LI, Experiment 1) and the partial reinforcement extinction effect (PREE, Experiment 2) paradigms. In LI, animals receiving prior nonreinforced preexposure to a stimulus (PE) show subsequently retarded conditioning to that stimulus as compared to nonpreexposed (NPE) controls. In the PREE, partially reinforced (PRF) animals exhibit higher resistance to extinction as compared to continuously reinforced (CRF) controls. LI and PREE were obtained in the HG condition, but were impaired in NHG and HI animals. The pattern of impairment was different in the two conditions. The absence of LI in NHG males was due to increased suppression in the PE group, whereas in HI males, was due to decreased suppression in the NPE group. Likewise, the attenuation of the PREE in NHG males stemmed primarily from decreased resistance to extinction in the PRF group, whereas in HI males, it resulted from increased resistance to extinction in the CRF group. The combination of nonhandling and isolation led to the reinstatement of both LI and PREE: normal LI and PREE were obtained in the NHI animals. These results demonstrate that early rearing experience interacts with later experience differentially depending upon the later experience.

Age Factors↗
PubMed1990

Neural substrates of latent inhibition: the switching model.

Latent inhibition (LI) refers to decrement in conditioning to a stimulus as a result of its prior nonreinforced preexposure. It is a robust phenomenon that has been demonstrated in a variety of classical and instrumental conditioning procedures and in many mammalian species, including humans. The development of LI is considered to reflect decreased associability of, or attention to, stimuli that predict no significant outcome. The fact that LI is considered to be a reflection of attentional processes has become of increasing importance to neuroscientists who see LI as a convenient tool for measuring the effects of drug treatments and lesions on attention. The present article surveys the data on brain systems, which have been studied in regard to their involvement in LI. These are reviewed and discussed separately in sections on noradrenergic, cholinergic, dopaminergic, serotonergic, and septo-hippocampal manipulations. On the basis of these data, it is concluded that the neural substrates of LI include the mesolimbic dopaminergic system, the mesolimbic serotonergic system, and the hippocampus. It is proposed that the preexposed stimulus loses its capacity to affect behavior in conditioning, even though it predicts reinforcement, because the hippocampus inhibits the switching mechanism of the nucleus accumbens via the subiculum-accumbens pathway. This action of the hippocampus is modulated by the mesolimbic serotonergic system via its interactions with the hippocampal or mesolimbic dopaminergic systems, or both.

Animals↗
PubMed1989

The effects of amphetamine on a multitrial partial reinforcement extinction effect (PREE) in a runway.

Three experiments examined the effects of d-amphetamine (1 mg/kg) administration on the partial reinforcement extinction effect (PREE) using a multitrial procedure. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasi-random 50% schedule. All animals were then tested in extinction. Experiments 1 and 2 used 6 trials/day with an intertrial interval (ITI) of 5 min. In Experiment 1 the drug was administered only during acquisition, whereas in Experiment 2 it was administered throughout acquisition and extinction. Experiment 3 used 3 trials/day with a 20 min ITI. The drug was administered throughout acquisition and extinction. In all three experiments, amphetamine-treated animals showed a normal PREE, i.e., increased resistance to extinction in PRF as compared to CRF animals. These results stand in marked contrast to the amphetamine-induced abolition of the PREE with 1 trial/day procedure.

Amphetamine↗
PubMed1989

The effects of amphetamine on a multitrial partial reinforcement extinction effect (PREE) in an operant chamber.

Two experiments investigated the effects of d-amphetamine (1 mg/kg) on the partial reinforcement extinction effect (PREE) in an operant chamber using a discrete multitrial procedure. Experiment 1 used a random 50% partial reinforcement (PRF) schedule. Experiment 2 used two 40% PRF schedules: one schedule maximized the number of nonreinforced trials preceding any given reinforced trial (maximum N-length of four) and the second maximized the number of N-R transitions (N-length of one). In both experiments, the continuously reinforced (CRF) animals received a reward on every trial. The PREE, i.e., increased resistance to extinction of PRF as compared to CRF animals, was obtained in the random 50% PRF and the schedule maximizing N-length in both the placebo and amphetamine-treated animals. Both drug and no-drug animals failed to exhibit PREE on the schedule maximizing N-R transitions. These results show that on a PRF schedule with short intertrial intervals, amphetamine-treated animals are not impaired in their capacity to learn sequences of events and to associate the outcomes of preceding trials with subsequent consequences.

Amphetamine↗
PubMed1989

Abolition of the acquisition but not the expression of latent inhibition by chlordiazepoxide in rats.

In the latent inhibition (LI) paradigm, prior nonreinforced exposure to a stimulus retards subsequent conditioning to that stimulus when it is paired with reinforcement. The development of LI reflects learning not to attend to, or ignore, stimuli which predict no significant consequences. The present experiment tested the effects of chlordiazepoxide (CDP) on LI using a conditioned emotional response (CER) procedure consisting of three stages given 24 hr apart: preexposure, in which the to-be-conditioned stimulus, tone, was presented without reinforcement; conditioning, in which the preexposed stimulus was paired with shock; and test, where LI was indexed by animals' suppression of licking during tone presentation. Preexposure and conditioning were given off-baseline. CDP (5 mg/kg) was administered only in preexposure, only in conditioning, in both stages or in neither. The administration of the drug during tone-shock conditioning conducted off-baseline markedly reduced animals' suppression to the tone in a subsequent licking test which was conducted without the drug. The administration of CDP during nonreinforced preexposure to the tone abolished the development of LI, i.e., drug-treated preexposed animals did not show reduced suppression as compared to drug-treated nonpreexposed animals. These results demonstrate that CDP: a) blocks the acquisition of classically conditioned fear and b) disrupts animals' ability to learn that stimuli predict no significant outcomes.

Animals↗
PubMed1988

The effects of haloperidol on the partial reinforcement extinction effect (PREE): implications for neuroleptic drug action on reinforcement and nonreinforcement.

The effects of haloperidol 0.1 mg/kg on the partial reinforcement extinction effect (PREE) paradigm at one trial a day, were examined. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasi-random 50% schedule. All animals were then tested in extinction. Haloperidol 0.1 mg/kg was administered in a 2 x 2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction of partially reinforced as compared to continuously reinforced animals, was obtained in all four drug conditions. The administration of haloperidol in acquisition increased markedly resistance to extinction in CRF animals. The administration of the drug in extinction decreased resistance to extinction in both CRF and PRF animals. The results are explained in terms of two independent actions of haloperidol: the well-known effect of reduction in the effectiveness of reinforcement as well as enhancement of the effectiveness of nonreinforcement.

Animals↗