Prepulse Inhibition of the Startle Reflex: A Window on the Brain in Schizophrenia

Braff, David L.

doi:10.1007/7854_2010_61

Cited by 106 publications

(97 citation statements)

References 118 publications

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“…Although a D2 antagonist impaired performance in rats with either profile, a D2 agonist impaired performance only in ST rats. Second, ST rats showed lower PPI than GT rats, revealing poorer sensorimotor gating in a task that requires dopamine receptor activation (Swerdlow et al, 2001;Braff, 2010). Third, rats with a NVHL, a developmental manipulation that alters corticolimbic dopamine functions, exhibited altered responses in ST rats, which performed poorer than sham controls, and increased sensibility to D2 blockade in GT rats.…”

Section: Discussionmentioning

confidence: 98%

Dopamine D2 Modulation of Sign and Goal Tracking in Rats

López

Karlsson

O’Donnell

2015

Neuropsychopharmacol

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In Pavlovian conditioning, sign-and goal-tracking behaviors represent different approaches towards the conditioned stimulus. These behavioral patterns have been associated with predictive or incentive properties of the conditioned stimulus, with a crucial involvement of the mesolimbic dopamine system. As it is possible that sign tracking behavior is more sensitive to dopamine modulation, we evaluated the dopamine-dependence of sign-and goal-tracking behavior. We assessed responses to both a D2 agonist and an antagonist, and tested performance in a behavioral paradigm known to activate dopamine projections and in an animal model that affects mesolimbic and mesocortical function. Sign trackers displayed a greater sensitivity to a D2 agonist and smaller prepulse inhibition of the acoustic startle response than goal trackers, suggesting a reduced inhibitory ability. In addition, a neonatal ventral hippocampal lesion resulted in the loss of incentive salience of cues in sign trackers. Overall, these data indicate that sign-tracking behavior is more heavily controlled by dopamine than goal tracking.

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Section: Discussionmentioning

confidence: 98%

Dopamine D2 Modulation of Sign and Goal Tracking in Rats

López

Karlsson

O’Donnell

2015

Neuropsychopharmacol

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“…In terms of the brain regions mediating the interactions between the M 1 mAChR PAM and antipsychotics in our models, it is likely that cortical and striatal regions are involved in the PPI effects, since they express the M 1 mAChR (Han et al, 2008;Ma et al, 2009;Peng et al, 2012) and have been implicated in regulation of sensorimotor gating mechanisms (Swerdlow et al, 1990Geyer et al, 2001;Braff, 2010). Although the M 1 mAChR is also found in the hippocampus, it is unlikely to be as important in the observed effects, as MK-801-induced PPI disruption does not involve this region and, if anything, cholinergic activation in the hippocampus can itself lead to some PPI disruption (Caine et al, 1991(Caine et al, , 1992Zhang et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Positive Allosteric Modulation of the Muscarinic M₁Receptor Improves Efficacy of Antipsychotics in Mouse Glutamatergic Deficit Models of Behavior

Choy

Shackleford

Malone

et al. 2016

J Pharmacol Exp Ther

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Current antipsychotics are effective in treating the positive symptoms associated with schizophrenia, but they remain suboptimal in targeting cognitive dysfunction. Recent studies have suggested that positive allosteric modulation of the M 1 muscarinic acetylcholine receptor (mAChR) may provide a novel means of improving cognition. However, very little is known about the potential of combination therapies in extending coverage across schizophrenic symptom domains. This study investigated the effect of the M 1 mAChR positive allosteric modulator BQCA [1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid], alone or in combination with haloperidol (a first-generation antipsychotic), clozapine (a second-generation atypical antipsychotic), or aripiprazole (a third-generation atypical antipsychotic), in reversing deficits in sensorimotor gating and spatial memory induced by the N-methyl-D-aspartate receptor antagonist, MK-801 [(5R,10S)-(1)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine]. Sensorimotor gating and spatial memory induction are two models that represent aspects of schizophrenia modeled in rodents. In prepulse inhibition (an operational measure of sensorimotor gating), BQCA alone had minimal effects but exhibited different levels of efficacy in reversing MK-801-induced prepulse inhibition disruptions when combined with a subeffective dose of each of the three (currently prescribed) antipsychotics. Furthermore, the combined effect of BQCA and clozapine was absent in M 1 2/2 mice. Interestingly, although BQCA alone had no effect in reversing MK-801-induced memory impairments in a Y-maze spatial test, we observed a reversal upon the combination of BQCA with atypical antipsychotics, but not with haloperidol. These findings provide proof of concept that a judicious combination of existing antipsychotics with a selective M 1 mAChR positive allosteric modulator can extend antipsychotic efficacy in glutamatergic deficit models of behavior.

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“…Elevated dopamine level as a common factor in these disorders means that behavioral manifestations of OCD, such as stereotypy, are not always specific to this disorder (Albelda and Joel 2012b). Thus, the greatest limitation of animal models is that it can be difficult to differentiate the psychiatric causes of their stereotypies (Albelda and Joel 2012a;Braff 2010;Featherstone et al 2007). The disorders are treated separately in human patients; in fact, obsessive-compulsive symptoms often surface during antipsychotic treatment of schizophrenic patients (Tibbo and Warneke 1999), although it is not known if the symptoms are unmasked, or are formed de novo (Ertugrul et al 2005).…”

Section: Limitations Of Animal Models In Studying Human Stereotypymentioning

confidence: 96%

Stereotypies in Captive Primates and the Use of Inositol: Lessons from Obsessive–Compulsive Disorder in Humans

Fam

Tan²,

Waitt

2012

Int J Primatol

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Animal stereotypies have long been used in the study of obsessive-compulsive disorder (OCD) in humans. These studies have led to the understanding of some of the molecular pathways in the disorder and the use of selective serotonin reuptake inhibitors and myo-inositol in the treatment of these conditions. If animal models, especially nonhuman primate models, were used to study human disorders and if the resulting treatments were successful, then conversely one should be able to treat nonhuman primate stereotypies with similar methods. We here summarize animal models of OCD (including nonhuman primate models) and human OCD treatments, and using successful human treatment by myo-inositol as models, recommend the use of myo-inositol in good captive management practice and the treatment of nonhuman primate stereotypies. We believe that this would be particularly useful in the treatment of stereotypies in nonhuman primates because they are physiologically so similar to humans.

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Prepulse Inhibition of the Startle Reflex: A Window on the Brain in Schizophrenia

Cited by 106 publications

References 118 publications

Dopamine D2 Modulation of Sign and Goal Tracking in Rats

Dopamine D2 Modulation of Sign and Goal Tracking in Rats

Positive Allosteric Modulation of the Muscarinic M₁Receptor Improves Efficacy of Antipsychotics in Mouse Glutamatergic Deficit Models of Behavior

Stereotypies in Captive Primates and the Use of Inositol: Lessons from Obsessive–Compulsive Disorder in Humans

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Prepulse Inhibition of the Startle Reflex: A Window on the Brain in Schizophrenia

Cited by 106 publications

References 118 publications

Dopamine D2 Modulation of Sign and Goal Tracking in Rats

Dopamine D2 Modulation of Sign and Goal Tracking in Rats

Positive Allosteric Modulation of the Muscarinic M1Receptor Improves Efficacy of Antipsychotics in Mouse Glutamatergic Deficit Models of Behavior

Stereotypies in Captive Primates and the Use of Inositol: Lessons from Obsessive–Compulsive Disorder in Humans

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Positive Allosteric Modulation of the Muscarinic M₁Receptor Improves Efficacy of Antipsychotics in Mouse Glutamatergic Deficit Models of Behavior