Human post-mortem striatal α4β2 nicotinic acetylcholine receptor density in schizophrenia and Parkinson's syndrome

Durany, Núria; Zöchling, Robert; Boissl, Karl W.; Paulus, Werner; Ransmayr, Gerhard; Tatschner, Thomas; Danielczyk, W; Jellinger, K. A.; Deckert, Jürgen; Riederer, Peter

doi:10.1016/s0304-3940(00)01144-7

Cited by 104 publications

(62 citation statements)

References 19 publications

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“…Impaired response inhibition has frequently been described in schizophrenia (Roberts and Pennington, 1996;Badcock et al, 2002;Henik et al, 2002) and is associated with abnormal striatal activation in both those with schizophrenia and their first-degree relatives (Vink et al, 2006). Deficient nAChR function in the cortex and caudate, with abnormal upregulation of a4 b2 nAChR's in these regions, have also been described in schizophrenia (Breese et al, 2000;Durany et al, 2000). Nicotine administration may ameliorate deficits in response inhibition in individuals with schizophrenia more than controls by augmenting deficient nAChR function, thereby increasing dopaminergic activity in regions important for this process.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Transdermal Nicotine on Cognition in Nonsmokers with Schizophrenia and Nonpsychiatric Controls

Barr

Culhane

Jubelt

et al. 2007

Neuropsychopharmacol

215

151

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Abundant evidence indicates that the neuronal nicotinic acetylcholine receptor (nAChR) system is integral to regulation of attentional processes and is dysregulated in schizophrenia. Nicotinic agonists may have potential for the treatment of cognitive impairment in this disease. This study investigated the effects of transdermal nicotine on attention in individuals with schizophrenia (n ¼ 28) and healthy controls (n ¼ 32). All participants were nonsmokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement that may occur in the study of smokers. Subjects received 14 mg transdermal nicotine and identical placebo in a randomized, placebocontrolled, crossover design. A cognitive battery was conducted before and 3 h after each patch application. The primary outcome measure was performance on the Continuous Performance Test Identical Pairs (CPT-IP) Version. Nicotine significantly improved the performance on the CPT-IP as measured by hit reaction time, hit reaction time standard deviation and random errors in both groups. In addition, nicotine reduced commission errors on the CPT-IP and improved the performance on a Card Stroop task to a greater extent in those with schizophrenia vs controls. In summary, nicotine improved attentional performance in both groups and was associated with greater improvements in inhibition of impulsive responses in subjects with schizophrenia. These results confirm previous findings that a single dose of nicotine improves attention and suggest that nicotine may specifically improve response inhibition in nonsmokers with schizophrenia.

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Section: Discussionmentioning

confidence: 99%

The Effects of Transdermal Nicotine on Cognition in Nonsmokers with Schizophrenia and Nonpsychiatric Controls

Barr

Culhane

Jubelt

et al. 2007

Neuropsychopharmacol

215

151

View full text Add to dashboard Cite

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“…In rodents, a4b2 subunit of nAChRs, but not a7, appears to regulate acoustic PPI (Schreiber et al, 2002). However, there is strong evidence suggesting that a7 nAChR (for a recent review see Martin and Freedman, 2007) and to a lesser extent a4b2 nAChR (Breese et al, 2000;Durany et al, 2000;Marutle et al, 2001;Faraone et al, 2004;De Luca et al, 2006) are involved in the pathology of schizophrenia. Subtype-specific nAChRs compounds are now becoming available for human studies.…”

Section: Discussionmentioning

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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“…Nicotinic receptor deficits have been shown to be key in the cognitive impairments of Alzheimer's disease (Nordberg and Winblad, 1986;Shimohama et al, 1986;Whitehouse et al, 1988;Giacobini et al, 1989;London et al, 1989;Kellar and Wonnacott, 1990;Rinne et al, 1991;Perry et al, 1995) and schizophrenia (Durany et al, 2000;Leonard et al, 2000). Nicotine delivered through means other than smoking such as transdermal patches may prove to be a safe and effective treatment for cognitive impairment seen in Alzheimer's disease, schizophrenia and attention deficit hyperactivity disorder (ADHD) and other types of cognitive dysfunction (Wilson et al, 1995;Levin et al, 1996b;Levin et al, 1996d;Newhouse et al, 1997;White and Levin, 1999).…”

Section: Introductionmentioning

confidence: 99%

Nicotinic receptor subtypes and cognitive function

2002

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ABSTRACT:Nicotinic receptor systems are involved in a wide variety of behavioral functions including cognitive function. Nicotinic medications may provide beneficial treatment for cognitive dysfunction such as Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Nicotine has been shown to improve attentional performance in all of these disorders. Better efficacy with fewer side effects might be achieved with novel nicotinic ligands selective for particular nicotinic subtypes. To develop these novel selective nicotinic ligands it is important to use animal models to determine the critical neurobehavioral bases for nicotinic involvement in cognitive function. Nicotineinduced cognitive improvement in rats is most consistently seen in working memory tasks. We have found that both acute and chronic nicotine administration significantly improves working memory performance of rats in the radial-arm maze. The pharmacologic and anatomic mechanisms for this effect have been examined in our laboratory in a series of local drug infusion studies. Both ␣4␤2 and ␣7 nicotinic receptors in the ventral hippocampus and basolateral amygdala are involved in working memory function. Working memory impairments were caused by local infusion of either ␣4␤2 or ␣7 antagonists. Ventral hippocampal ␣4␤2 blockade-induced working memory deficits are reversed by chronic systemic nicotine treatment, while ventral hippocampal ␣7 blockade-induced working memory deficits were not found to be reversed by the same nicotine regimen. Interestingly, ␣4␤2 and ␣7 induced deficits were not found to be additive in either the ventral hippocampus or the basolateral amygdala. In fact, in the amygdala, ␣7 antagonist cotreatment actually reversed the working memory impairment caused by ␣4␤2 antagonist administration. These studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction.

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Human post-mortem striatal α4β2 nicotinic acetylcholine receptor density in schizophrenia and Parkinson's syndrome

Cited by 104 publications

References 19 publications

The Effects of Transdermal Nicotine on Cognition in Nonsmokers with Schizophrenia and Nonpsychiatric Controls

The Effects of Transdermal Nicotine on Cognition in Nonsmokers with Schizophrenia and Nonpsychiatric Controls

Nicotine Effect on Prepulse Inhibition and Prepulse Facilitation in Schizophrenia Patients

Nicotinic receptor subtypes and cognitive function

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