The effects of methylphenidate on prepulse inhibition during attended and ignored prestimuli among boys with attention-deficit hyperactivity disorder

Hawk, Larry W.; Yartz, Andrew R.; Pelham, William E.; Lock, Thomas M.

doi:10.1007/s00213-002-1235-7

Cited by 81 publications

(98 citation statements)

References 69 publications

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“…Panic Disorder can also be seen as one which patients suffer from impairments in inhibiting the processing of sensory and cognitive information related to anxiogenic stimuli. Similarly, boys diagnosed with attention-deficit hyperactivity disorder (ADHD) exhibit deficits in the attentional modulation of PPI, although they appear to be normal in the typical passive PPI paradigm used in most other studies (Hawk et al, 2003). Furthermore, as appears to be the case in panic disorder, effective treatment of ADHD with methylphenidate reverses the attentional deficit seen in the PPI paradigm (Hawk et al, 2003).…”

Section: Sensorimotor Gating Deficits In Psychiatric Disordersmentioning

confidence: 99%

“…Similarly, boys diagnosed with attention-deficit hyperactivity disorder (ADHD) exhibit deficits in the attentional modulation of PPI, although they appear to be normal in the typical passive PPI paradigm used in most other studies (Hawk et al, 2003). Furthermore, as appears to be the case in panic disorder, effective treatment of ADHD with methylphenidate reverses the attentional deficit seen in the PPI paradigm (Hawk et al, 2003). It should also be noted, however, that deficient PPI is not found in several other psychiatric disorders, including Parkinson's disease (Perriol et al, 2005), Alzheimer's disease (Hejl et al, 2004;Perriol et al, 2005), or unipolar depression Perry et al, 2004;Quednow et al, 2004).…”

Section: Sensorimotor Gating Deficits In Psychiatric Disordersmentioning

confidence: 99%

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The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

2006

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Prepulse inhibition (PPI) of startle is an operational measure of the pre-attentive filtering process known as sensorimotor gating. Originally identified in patients with schizophrenia, PPI deficits have been observed in multiple but not all psychiatric disorders. Thus, as with most signs and symptoms of psychiatric disorders, deficits in PPI cut across diagnostic categories. It remains unclear whether the diversity of disorders exhibiting deficient PPI bespeaks diagnostic overlaps or comorbidities. Given the recent focus on treatments for cognitive deficits of schizophrenia independently of treating psychosis, the relationship of PPI deficits to cognitive deficits becomes of interest. Although PPI cannot be considered to be a cognitive process per se, abnormalities in pre-attentive information processing may be predictive of or lead to complex cognitive deficits. Animal models of PPI deficits produced by dopamine agonists reliably predict existing antipsychotics. Nevertheless, since neither PPI nor cognitive deficits in schizophrenia are ameliorated by standard antipsychotics, current research is exploring the predictive value of non-dopaminergic PPI models in identifying treatments for gating disturbances independently of their relevance to specific disorders. Both PPI and cognitive deficits in schizophrenia patients are not reversed by first generation antipsychotics but may be attenuated by clozapine. Similarly, effects of glutamate antagonists on symptoms in patients and PPI in animals appear to be reduced by clozapine. Hence, treatment-induced reversals of deficits in PPI produced by glutamate antagonists may provide animal, and human, models to aid in the discovery of treatments of cognitive deficits in patients already treated with existing antipsychotics.

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Section: Sensorimotor Gating Deficits In Psychiatric Disordersmentioning

confidence: 99%

Section: Sensorimotor Gating Deficits In Psychiatric Disordersmentioning

confidence: 99%

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

2006

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“…A number of psychiatric illnesses with manifested dysfunction in attentional mechanisms are hypothesized to involve pathology of the NE system (AstonJones et al, 1999). PPI deficits can be seen in many of these conditions including attention-deficit-hyperactivity disorder (ADHD), schizophrenia, and post-traumatic stress disorder (PTSD); interestingly, with ADHD, this PPI disruption is seen only with attended-to prepulses Castellanos et al, 1996;Grillon et al, 1996;Hawk et al, 2003;Ornitz et al, 1992). Thus, clarifying the nature of PPI modulation by NE may further our understanding of how this system regulates functions that are relevant to the information processing-related deficits observed in these illnesses.…”

Section: Introductionmentioning

confidence: 99%

Disruption of Prepulse Inhibition after Stimulation of Central but not Peripheral α-1 Adrenergic Receptors

Alsene

Carasso²,

Connors

et al. 2006

Neuropsychopharmacol

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Prepulse inhibition (PPI) refers to the attenuation of startle when a weak prestimulus precedes the startling stimulus. PPI is deficient in several psychiatric illnesses involving poor sensorimotor gating. Previous studies indicate that a1 adrenergic receptors regulate PPI, yet the extent to which these effects are mediated by central vs peripheral receptors is unclear. The present studies compared the effects of intracerebroventricular (ICV) vs intraperitoneal (IP) delivery of several a1 receptor agonists on PPI. Male Sprague-Dawley rats received either cirazoline (0, 10, 25, 50 mg/5 ml), methoxamine (0, 30, 100 mg/5 ml), or phenylephrine (0, 3, 10, 30 mg/5 ml) ICV immediately before testing. Separate groups received either cirazoline (0, 0.25, 0.50, 0.75 mg/kg), methoxamine (0, 2, 5, 10 mg/kg), or phenylephrine (0, 0.1, 2.0 mg/kg) IP 5 min before testing. PPI, baseline startle responses, and piloerection, an index of autonomic arousal, were measured. Cirazoline disrupted PPI; effective ICV doses were approximately six times lower than effective IP doses. Methoxamine disrupted PPI after ICV infusion but failed to affect PPI with IP doses that were up to 30-fold higher than the effective ICV dose. Phenylephrine disrupted PPI with ICV administration, but did not alter PPI after IP injection of even a 20-fold higher dose. None of the ICV treatments altered baseline startle magnitude, but phenylephrine and methoxamine lowered startle after administration of high systemic doses. Piloerection was induced by cirazoline via either route of administration, and by IP methoxamine and phenylephrine, but not by ICV infusion of methoxamine or phenylephrine. These findings indicate that a1 receptor-mediated PPI disruption occurs exclusively through stimulation of central receptors and is dissociable from alterations in baseline startle or autonomic effects.

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“…In PPI, the startle magnitude is reduced when the startle stimulus is preceded by a low-intensity prepulse (Koch, 1999;Swerdlow et al, 2000). In humans, disruption of PPI has been reported in schizophrenia (Braff et al, 2001) and ADHD (Hawk et al, 2003). In rodents, D-amph is used to pharmacologically disrupt PPI (Mansbach et al, 1988;Ralph et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Alpha2A-Adrenoceptors are Important Modulators of the Effects of D-Amphetamine on Startle Reactivity and Brain Monoamines

Lähdesmäki

Sallinen

MacDonald

et al. 2004

Neuropsychopharmacol

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Amphetamines are commonly used to treat attention-deficit hyperactivity disorder, but are also widely abused. They are employed in schizophrenia-related animal models as they disrupt the prepulse inhibition (PPI) of the acoustic startle response. The behavioral effects of amphetamines have mainly been attributed to changes in dopamine transmission, but they also involve increases in the synaptic concentrations of norepinephrine (NE). a 2 -Adrenoceptors (a 2 -ARs) regulate the excitability and transmitter release of brain monoaminergic neurons mainly as inhibitory presynaptic auto-and heteroreceptors. Modulation of acoustic startle and its PPI by the a 2A -AR subtype was investigated with mice lacking the a 2A -AR (a 2A -KO) and their wild-type (WT) controls, without drugs and after administration of the a 2 -AR agonist dexmedetomidine or the antagonist atipamezole. The interaction of D-amphetamine (D-amph) and the a 2 -AR-noradrenergic neuronal system in modulating startle reactivity and in regulating brain monoamine metabolism was assessed as the behavioral and neurochemical responses to D-amph alone, or to the combination of D-amph and dexmedetomidine or atipamezole. a 2A -KO mice were supersensitive to both neurochemical and behavioral effects of D-amph. Brain NE stores of a 2A -KO mice were depleted by D-amph, revealing the a 2A -AR as essential in modulating the actions of D-amph. Also, increased startle responses and more pronounced disruption of PPI were noted in D-amph-treated a 2A -KO mice. a 2A -AR also appeared to be responsible for the startlemodulating effects of a 2 -AR drugs, since the startle attenuation after the a 2 -AR agonist dexmedetomidine was absent in a 2A -KO mice, and the a 2 -AR antagonist atipamezole had opposite effects on the startle reflex in a 2A -KO and WT mice.

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The effects of methylphenidate on prepulse inhibition during attended and ignored prestimuli among boys with attention-deficit hyperactivity disorder

Abstract: These data are consistent with the hypothesis that ADHD involves diminished selective attention and suggest that methylphenidate ameliorates the symptoms of ADHD, at least in part, by altering an early attentional mechanism.

Cited by 81 publications

References 69 publications

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

Disruption of Prepulse Inhibition after Stimulation of Central but not Peripheral α-1 Adrenergic Receptors

Alpha2A-Adrenoceptors are Important Modulators of the Effects of D-Amphetamine on Startle Reactivity and Brain Monoamines

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