Abnormally persistent latent inhibition induced by MK801 is reversed by risperidone and by positive modulators of NMDA receptor function: differential efficacy depending on the stage of the task at which they are administered

Gaisler‐Salomon, Inna; Diamant, L.; Rubin, Cindy J.; Weiner, Ina

doi:10.1007/s00213-007-0960-3

Cited by 35 publications

(35 citation statements)

References 99 publications

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“…In this model, AVE1625 reversed neurodevelopmentally induced abnormally persistent LI. Previous studies using the L-NoArg model have shown that the abnormal behaviors in this model are reversed by procognitive agents and atypical antipsychotics Black et al 2009;Gaisler-Salomon and Weiner 2003;Gaisler-Salomon et al 2008). Such activity therefore strengthens the case for AVE1625 as a potentially effective treatment in the cognitive domain of schizophrenia.…”

Section: Discussionmentioning

confidence: 62%

“…Reversal of NMDA antagonist-induced abnormally persistent LI is believed to reflect potential therapeutic activity for negative symptoms of schizophrenia and Gaisler-Salomon and Weiner 2003;Gaisler-Salomon et al 2008). In this model, AVE1625 attenuated MK-801-induced persistent LI, therefore further supporting a potential procognitive profile for AVE1625.…”

Section: Discussionmentioning

confidence: 99%

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AVE1625, a cannabinoid CB1 receptor antagonist, as a co-treatment with antipsychotics for schizophrenia: improvement in cognitive function and reduction of antipsychotic-side effects in rodents

et al. 2010

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

AVE1625, a cannabinoid CB1 receptor antagonist, as a co-treatment with antipsychotics for schizophrenia: improvement in cognitive function and reduction of antipsychotic-side effects in rodents

et al. 2010

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“…Although the precise mechanisms underlying the effects of SSR180711 seen here remain to be investigated, our results demonstrate that this agent possesses in the LI model a behavioral profile of atypical APDs, which consists of LI potentiation when given on their own, reversal of amphetamine-induced disrupted LI and reversal of MK801-induced persistent LI (Gaisler-Salomon et al, 2008;Gaisler-Salomon and Weiner, 2003;Lipina et al, 2005;Shadach et al, 2000;Weiner, 2003). This is unlike the typical APDs, which fail to reverse MK801-induced LI persistence.…”

Section: Ssr180711-behavioral and Psychological Profilementioning

confidence: 52%

Pro-Cognitive and Antipsychotic Efficacy of the α7 Nicotinic Partial Agonist SSR180711 in Pharmacological and Neurodevelopmental Latent Inhibition Models of Schizophrenia

Barak

Arad

Levie

et al. 2009

Neuropsychopharmacol

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Schizophrenia symptoms can be segregated into positive, negative and cognitive, which exhibit differential sensitivity to drug treatments. Accumulating evidence points to efficacy of a7 nicotinic receptor (nAChR) agonists for cognitive deficits in schizophrenia but their activity against positive symptoms is thought to be minimal. The present study examined potential pro-cognitive and antipsychotic activity of the novel selective a7 nAChR partial agonist SSR180711 using the latent inhibition (LI) model. LI is the reduced efficacy of a previously nonreinforced stimulus to gain behavioral control when paired with reinforcement, compared with a novel stimulus. Here, no-drug controls displayed LI if non-reinforced pre-exposure to a tone was followed by weak but not strong conditioning (2 vs 5 tone-shock pairings). MK801 (0.05 mg/kg, i.p.) -treated rats as well as rats neonatally treated with nitric oxide synthase inhibitor L-NoArg (10 mg/kg, s.c.) on postnatal days 4-5, persisted in displaying LI with strong conditioning, whereas amphetamine (1 mg/kg) -treated rats failed to show LI with weak conditioning. SSR180711 (0.3, 1, 3 mg/kg, i.p.) was able to alleviate abnormally persistent LI produced by acute MK801 and neonatal L-NoArg; these models are believed to model cognitive aspects of schizophrenia and activity here was consistent with previous findings with a7-nAChR agonists. In addition, unexpectedly, SSR180711 (1, 3 mg/kg, i.p.) potentiated LI with strong conditioning in nodrug controls and reversed amphetamine-induced LI disruption, two effects considered predictive of activity against positive symptoms of schizophrenia. These findings suggest that SSR180711 may be beneficial not only for the treatment of cognitive symptoms in schizophrenia, as reported multiple times previously, but also positive symptoms.

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“…For example, blockade of NMDA receptors during conditioning results in persistent latent inhibition (i.e., latent inhibition is expressed under conditions in which stronger conditioning typically overcomes the effects of CS pre-exposure) (Gaisler-Salomon and Weiner 2003). DCS injected before conditioning effectively disrupts this persistent latent inhibition induced by blockade of NMDA receptors (Gaisler-Salomon et al 2008). Nonetheless, there was no evidence here to support the possibility that learned inattention to the CS is causal to DCS facilitation of extinction retention.…”

Section: Discussionmentioning

confidence: 79%

d-cycloserine does not facilitate fear extinction by reducing conditioned stimulus processing or promoting conditioned inhibition to contextual cues

2012

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The NMDA receptor partial agonist D-cycloserine (DCS) enhances the extinction of learned fear in rats and exposure therapy in humans with anxiety disorders. Despite these benefits, little is known about the mechanisms by which DCS promotes the loss of fear. The present study examined whether DCS augments extinction retention (1) through reductions in conditioned stimulus (CS) processing or (2) by promoting the development of conditioned inhibition to contextual cues. Rats administered DCS prior to extinction showed enhanced long-term extinction retention (Experiments 3 and 4). The same nonreinforced CS procedure used in extinction also reduced freezing at test when presented as pre-exposure before conditioning, demonstrating latent inhibition (Experiment 1). DCS administered shortly prior to pre-exposure had no effect on latent inhibition using parameters which produced weak (Experiment 2) or strong (Experiment 3) expression of latent inhibition. Therefore, DCS facilitated learning involving CS-alone exposures, but only when these exposures occurred after (extinction) and not before (latent inhibition) conditioning. We also used a retardation test procedure to examine whether the extinction context gained inhibitory properties for rats given DCS prior to extinction. With three different footshock intensities, there was no evidence that DCS promoted accrual of associative inhibition to the extinction context (Experiment 4). The present findings demonstrate that DCS does not facilitate extinction by reducing CS processing or causing the extinction context to become a conditioned inhibitor. Investigations into the mechanisms underlying the augmentation of extinction by DCS are valuable for understanding how fear can be inhibited.

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Abnormally persistent latent inhibition induced by MK801 is reversed by risperidone and by positive modulators of NMDA receptor function: differential efficacy depending on the stage of the task at which they are administered

Cited by 35 publications

References 99 publications

AVE1625, a cannabinoid CB1 receptor antagonist, as a co-treatment with antipsychotics for schizophrenia: improvement in cognitive function and reduction of antipsychotic-side effects in rodents

AVE1625, a cannabinoid CB1 receptor antagonist, as a co-treatment with antipsychotics for schizophrenia: improvement in cognitive function and reduction of antipsychotic-side effects in rodents

Pro-Cognitive and Antipsychotic Efficacy of the α7 Nicotinic Partial Agonist SSR180711 in Pharmacological and Neurodevelopmental Latent Inhibition Models of Schizophrenia

d-cycloserine does not facilitate fear extinction by reducing conditioned stimulus processing or promoting conditioned inhibition to contextual cues

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