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

Lacroix, Laurent; Spinelli, Simona; White, Wesley; Feldon, Joram

doi:10.1016/s0306-4522(00)00013-0

Cited by 73 publications

(37 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data could be interpreted to mean the prelimbic/ infralimbic subregion of the PFC is involved in the latent inhibition phenomenon, which would be consistent with recent studies carried out with focal lesions in adults (George et al, 2010;Nelson et al, 2010), rather than previous works performed with more dorsal lesioning sites in the anteromedian PFC (Lacroix et al, 2000;Schiller and Weiner, 2004). However, lesions in the prelimbic/infralimbic subregion of the PFC in adults resulted in enhanced latent inhibition (George et al, 2010;Nelson et al, 2010), whereas what we observed was that latent inhibition disappeared after postnatal TTX microinjection in the same PFC subregion, suggesting that different mechanisms are involved after intervention in adults and during the postnatal developmental period.…”

Section: Neonatal Prefrontal Blockade Consequencessupporting

confidence: 90%

Early Prefrontal Functional Blockade in Rats Results in Schizophrenia-Related Anomalies in Behavior and Dopamine

Meyer

Louilot

2012

Neuropsychopharmacol

View full text Add to dashboard Cite

Growing evidence suggests schizophrenia may arise from abnormalities in early brain development. The prefrontal cortex (PFC) stands out as one of the main regions affected in schizophrenia. Latent inhibition, an interesting cognitive marker for schizophrenia, has been found in some studies to be reduced in acute patients. It is generally widely accepted that there is a dopaminergic dysfunctioning in schizophrenia. Moreover, several authors have reported that the psychostimulant, D-amphetamine (D-AMP), exacerbates symptoms in patients with schizophrenia. We explored in rats the effects in adulthood of neonatal transient inactivation of the PFC on behavioral and neurochemical anomalies associated with schizophrenia. Following tetrodotoxin (TTX) inactivation of the left PFC at postnatal day 8, latent inhibition-related dopaminergic responses and dopaminergic reactivity to D-AMP were monitored using in vivo voltammetry in the left core part of the nucleus accumbens in adult freely moving rats. Dopaminergic responses and behavioral responses were followed in parallel. Prefrontal neonatal inactivation resulted in disrupted behavioral responses of latent inhibition and latent inhibition-related dopaminergic responses in the core subregion. After D-AMP challenge, the highest dose (1.5 mg/kg i.p.) induced a greater dopamine increase in the core in rats microinjected with TTX, and a parallel increase in locomotor activity, suggesting that following prefrontal neonatal TTX inactivation animals display a greater behavioral and dopaminergic reactivity to D-AMP. Transitory inactivation of the PFC early in the postnatal developmental period leads to behavioral and neurochemical changes in adulthood that are meaningful for schizophrenia modeling. The data obtained may help our understanding of the pathophysiology of this disabling disorder.

show abstract

Section: Neonatal Prefrontal Blockade Consequencessupporting

confidence: 90%

Early Prefrontal Functional Blockade in Rats Results in Schizophrenia-Related Anomalies in Behavior and Dopamine

Meyer

Louilot

2012

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…In the present study, it is shown that the hyperactivity to novelty induced by social isolation is not correlated with changes in the in vivo function and binding of D2 receptors in dorsal/ventral striatum, which supports the hypothesis that the changes in the motor activity, as well as other behavioral disturbances, induced by rearing rats in isolation are part of a more complex syndrome which probably involves a new neurochemical balance in the interaction of multiple neurotransmitter systems in different areas of the brain (Robbins et al 1996;Heidbreder et al 2000). For instance, since lesions in the prefrontal cortex can induce hyperactivity (Lacroix et al 2000) and enhance nucleus accumbens dopamine function (Brake et al 2000), changes in prefrontal cortex function may be involved in the behavioral and neurochemical changes observed in isolated rats (Heidbreder et al 2000;Dalley et al 2002).…”

Section: Discussionsupporting

confidence: 64%

Hyperactivity to novelty induced by social isolation is not correlated with changes in D2 receptor function and binding in striatum

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Although there is evidence for a close link between PFC DA activity and PPI in rodents (Bubser and Koch, 1994;Ellenbroek et al, 1996;Zavitsanou et al, 1999;Broersen et al, 1999;Lacroix et al, 2000) and the importance of PFC for PPI modulation in humans is rapidly accumulating (see 'Introduction'), PPI is regulated by a complex cortico-striato-pallido-pontine circuit (Swerdlow et al, 1992(Swerdlow et al, , 2001, in which the PFC is only one critical node. For instance, COMT is also expressed in the hippocampus (Matsumoto et al, 2003), which is also involved in PPI modulation (Swerdlow et al, 2001) and it is not known how COMT inhibition by tolcapone within the hippocampus may have influenced our results.…”

Section: Discussionmentioning

confidence: 99%

Improvement of Prepulse Inhibition and Executive Function by the COMT Inhibitor Tolcapone Depends on COMT Val158Met Polymorphism

Giakoumaki

Roussos

Bitsios

2008

Neuropsychopharmacol

129

105

View full text Add to dashboard Cite

Recent evidence suggests that prepulse inhibition (PPI) levels relate to executive function possibly by a prefrontal cortex (PFC) dopamine (DA) link. We explored the effects of enhanced PFC DA signaling by the nonstimulant catechol-O-methyltransferase (COMT) inhibitor tolcapone, on PPI and working memory of subjects homozygous for the Val (low PFC DA) and the Met (high PFC DA) alleles of the COMT Val158Met polymorphism. Twelve Val/Val and eleven Met/Met healthy male subjects entered the study. Tolcapone 200 mg was administered in two weekly sessions, according to a balanced, crossover, double-blind, placebo-controlled design. PPI was assessed with 5 dB and 15 dB above background prepulses, at 30-, 60-, and 120 ms prepulse-pulse intervals. Subjects also underwent the n-back and the letter-number sequencing (LNS) tasks. PPI was lower in the Val/Val compared to the Met/Met group in the placebo condition. Tolcapone increased PPI significantly in the Val/Val group and tended to have the opposite effect in the Met/Met group. Baseline startle was not affected by tolcapone in the Val/Val group but it was slightly increased in the Met/Met group. Tolcapone improved performance in the n-back and LNS tasks only in the Val/Val group. Enhancement of PFC DA signaling with tolcapone improves both PPI and working memory in a COMT Val158Met genotype-specific manner. These results suggest that early information processing and working memory may both depend on PFC DA signaling, and that they may both relate to PFC DA levels according to an inverted U-shaped curve function. Neuropsychopharmacology (2008) 33, 3058-3068; doi:10.1038/npp.2008 published online 4 June 2008 Keywords: prepulse inhibition; sensorimotor gating; prefrontal cortex; dopamine; cognition; working memory INTRODUCTIONThe enzyme catechol-O-methyltransferase (COMT) is the main catabolic pathway by which dopamine (DA) is removed from the cortical synaptic cleft in humans (Karoum et al, 1994). Indeed, COMT is found in high concentrations in the cortex relative to subcortical regions (Matsumoto et al, 2003) consistent with the absence of functional DA transporters in cortical areas such as the prefrontal cortex (PFC) and hippocampus (Mazei et al, 2002). The Val158Met polymorphism in the COMT gene leads to an amino-acid substitution (valine (Val) to methionine (Met)) and results in the Met/Met variant showing 40% less enzymatic activity than the Val/Val (Chen et al, 2004). There is now abundant evidence (reviewed in Harrison and Weinberger, 2005;Tunbridge et al, 2006) that Met158 allele loading is dose dependently associated with superior performance on a variety of cognitive tests assessing executive function, as well as prefrontal physiology as assessed by neuroimaging. The evidence suggests that PFC DA facilitates 'focusing and stabilizing' activity in PFC networks during executive cognition, ie enhances prefrontal physiologic 'efficiency' by reduction of prefrontal noise (Cools et al, 2002;Mattay et al, 2002Mattay et al, , 2003.Prepulse inhibition (PPI) is thought...

show abstract

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

Cited by 73 publications

References 94 publications

Early Prefrontal Functional Blockade in Rats Results in Schizophrenia-Related Anomalies in Behavior and Dopamine

Early Prefrontal Functional Blockade in Rats Results in Schizophrenia-Related Anomalies in Behavior and Dopamine

Hyperactivity to novelty induced by social isolation is not correlated with changes in D2 receptor function and binding in striatum

Improvement of Prepulse Inhibition and Executive Function by the COMT Inhibitor Tolcapone Depends on COMT Val158Met Polymorphism

Contact Info

Product

Resources

About