Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics

Adler, Lawrence E.; Hoffer, Lee; Griffith, Jenny; Waldo, Merilyne; Freedman, Robert

doi:10.1016/0006-3223(92)90073-9

Cited by 392 publications

(228 citation statements)

References 31 publications

Supporting

Mentioning

211

Contrasting

Unclassified

Order By: Relevance

“…A likely possibility is that the effects are mediated by modulation of the cholinergic system. A link between P50 suppression and nicotinic receptors has been reported previously (Adler et al, 1986(Adler et al, , 1992Freedman et al, 1997), and tropisetron has been shown to modulate P50 suppression via effects on nicotinic receptors .…”

Section: Serotonin Depletionmentioning

confidence: 63%

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Mann

Croft

Scholes

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

Schizophrenia is associated with impairments of sensorimotor and sensory gating as measured by prepulse inhibition (PPI) of the acoustic startle response and P50 suppression of the auditory event-related potential respectively. While serotonin and dopamine play an important role in the pathophysiology and treatment of schizophrenia, their role in modulating PPI and P50 suppression in humans is yet to be fully clarified. To further explore the role of serotonin and dopamine in PPI and P50 suppression, we examined the effects of acute tryptophan depletion (to decrease serotonin) and acute tyrosine/phenylalanine depletion (to decrease dopamine) on PPI and P50 suppression in healthy human participants. In addition, we also examined for the first time, the effects of simultaneous serotonin and dopamine depletion (ie combined monoamine depletion) on PPI and P50 suppression. The study was a double-blind, placebo-controlled cross-over design in which 16 healthy male participants completed the PPI and P50 paradigms under four acute treatment conditions: (a) balanced/placebo control, (b) acute tryptophan depletion, (c) acute tyrosine/phenylalanine depletion, and (d) acute tyrosine/ phenylalanine/tryptophan depletion (combined monoamine depletion). Selective depletion of dopamine had no significant effect on either PPI or P50 suppression, whereas selective serotonin depletion significantly disrupted PPI, but not P50 suppression. Finally, the simultaneous depletion of both serotonin and dopamine resulted in significant reduction of both PPI and P50 suppression. We suggest these results can be explained by theories relating to optimal levels of monoaminergic neurotransmission and synergistic interactions between serotonergic and dopaminergic systems for normal 'gating' function. These findings suggest that a dysfunction in both serotonin and dopamine neurotransmission may, in part, be responsible for the gating deficits observed in schizophrenia, and their normalization following administration of atypical antipsychotic drugs.

show abstract

Section: Serotonin Depletionmentioning

confidence: 63%

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Mann

Croft

Scholes

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…While it could be hypothesized that the nicotinic receptors are not desensitized in schizophrenics and therefore fail to upregulate, data showing a transient effect of nicotine on the normalization of the abnormal auditory gating response in schizophrenics do not support this hypothesis (Adler et al 1992(Adler et al , 1993. Nevertheless, schizophrenics could have an abnormality in any of several potential mechanisms that change the desensitization state of the receptor and receptor turnover, as well as activation and ion flux through the receptor.…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, it has been shown that abnormal electro- NO . 4 physiological and eye-tracking deficits can be normalized by cigarette smoking or nicotine administration (Adler et al 1992(Adler et al , 1993Olincy et al 1998). Smoking may also alleviate neuroleptic-induced extrapyramidal side effects (Decina et al 1990;Goff et al 1992;Sandyk 1993).…”

mentioning

confidence: 99%

Abnormal Regulation of High Affinity Nicotinic Receptors in Subjects with Schizophrenia

Breese

2000

Neuropsychopharmacology

304

215

View full text Add to dashboard Cite

Previous studies have suggested that an abnormality in neuronal nicotinic acetylcholine receptor expression or function may be involved in the neuropathophysiology of schizophrenia. [ 3 H]-nicotine and [ 3 H]-epibatidine binding were compared in postmortem brain from control and schizophrenic subjects with varying smoking histories. In control subjects, increased receptor binding was seen in hippocampus, cortex, and caudate with increasing tobacco use. In contrast, schizophrenic smokers had reduced nicotinic receptor levels in these brain regions compared to control smokers. Chronic haloperidol and nicotine treatment, in the rat, was used to assess neuroleptic effects on receptor up-regulation by nicotine. A significant increase in cortical nicotinic receptors was seen in both nicotine treated as well as haloperidol and nicotine co-treated animals, suggesting that the abnormal regulation of high affinity neuronal nicotinic receptors in schizophrenics followingPrevious studies have shown that high affinity nicotinic receptor numbers increase in the brains of human subjects who smoke (Benwell et al. 1988;Breese et al. 1997a;Court et al. 1998). This increase was shown to be dosedependent, based on the number of cigarettes smoked at death, and was reversible, with binding levels returning to control values in subjects who had quit smoking for at least two months prior to death (Breese et al. 1997a). The up-regulation of receptor numbers does not appear to be under transcriptional regulation (Marks et al. 1992). Rather, the increases may be related to changes in receptor turnover based on receptor desensitization, subunit composition, secondary structural changes in the receptor, or to modification of the receptor by protein kinases (Peng et al. 1994;Baenziger and Chew 1997;Eilers et al. 1997;Flores et al. 1997;Hsu et al. 1997;Xiao et al. 1998;Fenster et al. 1999).In spite of the high degree of nicotine self-administration in schizophrenics (Lohr and Flynn 1992;Ziedonis et al. 1994;de Leon et al. 1995), few studies have examined the effect of smoking or neuroleptic treatment on nicotinic receptor regulation in this disease (Dalack et al. 1998). It has been suggested that nicotine self-administration in schizophrenics may control a neuronal deficit. In this regard, it has been shown that abnormal electro- NO . 4 physiological and eye-tracking deficits can be normalized by cigarette smoking or nicotine administration (Adler et al. 1992(Adler et al. , 1993Olincy et al. 1998). Smoking may also alleviate neuroleptic-induced extrapyramidal side effects (Decina et al. 1990;Goff et al. 1992;Sandyk 1993). Nicotine use increases haloperidol metabolism (Jann et al. 1986;Miller et al. 1990), requiring patients that smoke to take higher doses than non-smoking schizophrenics, often further increasing their smoking behavior (McEvoy et al. 1995). Interestingly, clozapine, which does not induce the motor dysfunctions seen with typical neuroleptics, reduces smoking behavior (George et al. 1995) and normalizes the electrophysiologi...

show abstract

“…Because nicotine′s demonstrated modulatory effect on sensory gating lasts less than 60 minutes (Adler et al, 2001;Adler et al, 1992), recordings were not conducted until at least 1 hour after any participant had smoked. None of the smokers were recorded during a withdrawal period that exceeded normal daily routine (number of smokers = 5, 4, and 8 for auditory, somatosensory and combined studies respectively).…”

Section: Participantsmentioning

confidence: 99%

Gamma and beta neural activity evoked during a sensory gating paradigm: Effects of auditory, somatosensory and cross-modal stimulation

Kisley

Cornwell

2006

Clinical Neurophysiology

111

View full text Add to dashboard Cite

Objective.-Stimulus-driven salience is determined involuntarily, and by the physical properties of a stimulus. It has recently been theorized that neural coding of this variable involves oscillatory activity within cortical neuron populations at beta frequencies. This was tested here through experimental manipulation of inter-stimulus interval (ISI).Methods.-Non-invasive neurophysiological measures of event-related gamma (30-50 Hz) and beta (12-20 Hz) activity were estimated from scalp-recorded evoked potentials. Stimuli were presented in a standard "paired-stimulus" sensory gating paradigm, where the S1 (conditioning) stimulus was conceptualized as long-ISI, or "high salience," and the S2 (test) stimulus as short-ISI, or "low salience." Three separate studies were conducted: auditory stimuli only (N=20 participants), somatosensory stimuli only (N=20), and a cross-modal study for which auditory and somatosensory stimuli were mixed (N=40).Results.-Early (20-150 ms) stimulus-evoked beta activity was more sensitive to ISI than temporally-overlapping gamma band activity, and this effect was seen in both auditory and somatosensory studies. In the cross-modal study, beta activity was significantly modulated by the similarity (or dissimilarity) of stimuli separated by a short ISI (0.5 s); a significant cross-modal gating effect was nevertheless detected.Conclusions.-With regard to the early sensory-evoked response recorded from the scalp, the interval between identical stimuli especially modulates beta oscillatory activity.Significance.-This is consistent with developing theories regarding the different roles of temporally-overlapping oscillatory activity within cortical neuron populations at gamma and beta frequencies, particularly the claim that the latter is related to stimulus-driven salience.

show abstract

Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics

Cited by 392 publications

References 31 publications

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

Abnormal Regulation of High Affinity Nicotinic Receptors in Subjects with Schizophrenia

Gamma and beta neural activity evoked during a sensory gating paradigm: Effects of auditory, somatosensory and cross-modal stimulation

Contact Info

Product

Resources

About