Strain-Specificity in Nicotine Attenuation of Phencyclidine-Induced Disruption of Prepulse Inhibition in Mice: Relevance to Smoking in Schizophrenia Patients

Spielewoy, Cécile; Markou, Athina

doi:10.1023/b:bege.0000017878.75206.fd

Cited by 33 publications

(24 citation statements)

References 64 publications

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“…Studies in humans (Baschnagel and Hawk, 2008;Della Casa et al, 1998;Duncan et al, 2001;Hong et al, 2008;Kumari et al, 1996Kumari et al, , 1997 and animals (Acri et al, 1994(Acri et al, , 1995Curzon et al, 1994;Faraday et al, 1999;Schreiber et al, 2002;Spielewoy and Markou, 2004) have shown that the nicotinic acetylcholine receptor (nAChR) agonist, nicotine, enhances PPI. These findings, taken together with the idea that schizophrenia patients have a strongly increased likelihood of smoking (for reviews, see Dalack et al, 1998;Ripoll et al, 2004), have led to the 'self-medication hypothesis' that proposes that schizophrenia patients may attempt to transiently remedy otherwise deficient attentional processes; this effect, however, could vary depending on genetic background (Kumari and Postma, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…At present, it is still unclear whether genetic variation in the nAChR system could have an impact on human PPI. However, the PPI-enhancing effects of nicotine in rodents seem to be strain dependent, which points to a strong genetic modulation of this effect within the nAChR system (Curzon et al, 1994;Faraday et al, 1998Faraday et al, , 1999Schreiber et al, 2002;Spielewoy and Markou, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Sensorimotor Gating is Associated with CHRNA3 Polymorphisms in Schizophrenia and Healthy Volunteers

Petrovsky

Quednow

Ettinger

et al. 2010

Neuropsychopharmacol

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Attentional gating deficits, commonly measured by prepulse inhibition (PPI) of the acoustic startle response (ASR), have been established as an endophenotype of schizophrenia. Prepulse inhibition is heritable and has been associated with polymorphisms in serotonin and dopamine system genes. Prepulse inhibition can be enhanced by nicotine, and therefore it has been proposed that schizophrenia patients smoke to ameliorate their early attentional deficits. The PPI-enhancing effects of nicotine in rodents are strain dependent, suggesting a genetic contribution to PPI within the nicotinic acetylcholine receptor (nAChR) system. Recent human genetic studies also imply that tobacco dependence is affected by polymorphisms in the a3/a5 subunits of the nAChR (CHRNA3/CHRNA5) gene cluster. We, therefore, investigated the impact of two common CHRNA3 polymorphisms (rs1051730/rs1317286) on PPI, startle reactivity, and habituation of the ASR in two independent samples of 107 healthy British volunteers and 73 schizophrenia patients hailing from Germany. In both samples, PPI was influenced by both CHRNA3 polymorphisms (combined p-value ¼ 0.0027), which were strongly linked. Moreover, CHRNA3 genotype was associated with chronicity, treatment, and negative symptoms in the schizophrenia sample. These results suggest that sensorimotor gating is influenced by variations of the CHRNA3 gene, which might also have an impact on the course and severity of schizophrenia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sensorimotor Gating is Associated with CHRNA3 Polymorphisms in Schizophrenia and Healthy Volunteers

Petrovsky

Quednow

Ettinger

et al. 2010

Neuropsychopharmacol

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“…Animal studies have shown that nicotine enhances acoustic PPI in some rodent strains (Acri, 1994;Curzon et al, 1994;Acri et al, 1995;Faraday et al, 1999;Schreiber et al, 2002;Spielewoy and Markou, 2004); an effect thought to be mediated by nicotinic acetylcholine receptors (nAChRs) (Schreiber et al, 2002;Suemaru et al, 2004). However, other studies have shown no effect, or even the opposite effect (Decker et al, 1997;Faraday et al, 1999;Mirza et al, 2000;Schreiber et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…In some rodent strains, nicotine blocks PPI deficit induced by agents that modulate neurotransmitter systems putatively related to schizophrenia pathophysiology. These agents include the NMDA antagonist PCP and dopamine agonist apomorphine (Spielewoy and Markou, 2004;Suemaru et al, 2004;Andreasen et al, 2006). However, nicotinic effect on PPI in schizophrenia patients has not been sufficiently studied.…”

Section: Introductionmentioning

confidence: 99%

Nicotine Effect on Prepulse Inhibition and Prepulse Facilitation in Schizophrenia Patients

Hong

Wonodi

Lewis

et al. 2007

Neuropsychopharmacol

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Acoustic prepulse inhibition (PPI) is considered an important biomarker in animal studies of psychosis and a number of psychiatric conditions. Nicotine has been shown to improve acoustic PPI in some animal strains and in humans. However, there is little data on effects of nicotine on acoustic PPI in schizophrenia patients using a double-blind, placebo-controlled study design. The primary aim of the current study was to test the effect of nicotine nasal spray on acoustic PPI in schizophrenia patients. The secondary aim was to test nicotine effect on prepulse facilitation (PPF). The study included 18 schizophrenia patient smokers and 12 healthy control smokers, tested in a double-blind, placebo-controlled, crossover, randomized design immediately after nicotine or saline placebo nasal sprays. PPI was tested using 120 ms prepulse-pulse interval. PPF was tested using 4500 ms prepulse-pulse interval. The results showed a significant main effect of drug on PPI in that nicotine improved PPI compared to placebo (p ¼ 0.008) with no drug by diagnosis interaction (p ¼ 0.90). Improvement in PPI in response to nicotine was significantly correlated with the baseline severity of clinical symptoms (r ¼ 0.59, p ¼ 0.02) in patients. There was no significant drug or drug by diagnosis interaction for the 4500 ms prepulse-pulse interval condition. However, nicotine improved inhibition in a subgroup of subjects exhibiting PPF (p ¼ 0.002). In conclusion, the findings confirmed that nicotine transiently improves acoustic PPI in schizophrenia patients. Additionally, schizophrenia patients with more clinical symptoms may have benefited more from nicotinic effect on PPI.

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“…Nicotine, an agonist of nicotinic acetylcholine receptors (nAChR), consistently enhances PPI in humans (Baschnagel and Hawk 2008;Della Casa et al 1998;Duncan et al 2001; Kumari et al 1996;Kumari et al 1997) and animals (Acri et al 1995;Acri et al 1994;Curzon et al 1994;Faraday et al 1999;Schreiber et al 2002;Spielewoy and Markou 2004) The exact mechanism by which nicotine enhances PPI is not yet understood but one way nicotine may improve PPI is by enhancing the diminishment of the processing of the pulse suggesting that nicotine may improve stimulus filtering (Baschnagl and Hawk 2008). In mice, the PPI-enhancing effect of nicotine is strain dependent (Faraday et al 1999) suggesting genetic influences in nicotine-induced modulation of PPI (Kumari and Postma 2005).…”

Section: Introductionmentioning

confidence: 99%

The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism

et al. 2013

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RATIONALE: Prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating, can be enhanced by nicotine. Moreover, the TT genotype of the nicotinic acetylcholine receptor (nAChR) 3-subunit (CHRNA3) rs1051730 polymorphism has previously been associated with diminished PPI and nicotine dependence. OBJECTIVES: We tested whether this CHRNA3 polymorphism also modulates the nicotine-induced enhancement of PPI. METHODS: We assessed the effect of nicotine on PPI, startle reactivity, and habituation in 52 healthy nonsmoking volunteers genotyped for CHRNA3 rs1051730 in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Additionally, cotinine plasma levels were measured. RESULTS: Nicotine significantly enhanced PPI in TT homozygotes only and tended to worsen PPI in TC and CC carriers. Additionally, nicotine significantly reduced startle habituation. CONCLUSIONS: The present findings imply that the effect of nicotine on sensorimotor gating is modulated by nAChR 3-subunits. Thus, genetic variation in nicotinic receptor genes might be an important connecting link between early attentional processes and smoking behavior.

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Strain-Specificity in Nicotine Attenuation of Phencyclidine-Induced Disruption of Prepulse Inhibition in Mice: Relevance to Smoking in Schizophrenia Patients

Cited by 33 publications

References 64 publications

Sensorimotor Gating is Associated with CHRNA3 Polymorphisms in Schizophrenia and Healthy Volunteers

Sensorimotor Gating is Associated with CHRNA3 Polymorphisms in Schizophrenia and Healthy Volunteers

Nicotine Effect on Prepulse Inhibition and Prepulse Facilitation in Schizophrenia Patients

The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism

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