Schizophrenia nicotinic receptors

Martin LF, Kem WR, Freedman R. (2004) a-7 nicotinic receptor agonists Potential new candidates for the treatment of schizophrenia. Psychopharmacology 174 54-64. 

K.M., Marks, M.J., Collins, A.C., and Leonard, S. (2000) Abnormal regulation of high-affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology 23 351-364. 

Leonard S, Adams C, Breese CR, et al. Nicotinic receptor function in schizophrenia. Schizophr Buh 1996 22 431-445. 

Nicotinic receptor agonists have been developed in an attempt to further characterize central nervous system cholinergic function and as potential candidates for the treatment of schizophrenia. 

The aim of this study was to determine, as a proof of concept, if DMXB-A significantly improves neurocognition and to assess, by effects on P50 inhibition, whether its actions are consistent with activation of oc7-nicotinic receptors. Because the proposed effect is agonism at a ligand-gated ion channel, biological effects were expected immediately, consistent with the results from animal models (Stevens et al., 1998). Twelve persons with schizophrenia consented to the study. They were concurrently treated with neuroleptic medications. Subjects who had not used nicotine or tobacco within the last month were selected to avoid possible interaction with chronic nicotine exposure. DMXB-A was administered orally (150 or 75 mg) followed 2 h later by a half dose (75 or 37.5 mg). The half dose, administered at the predicted half-life of the... 

On each experimental day, the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) was administered (Randolph, 1998). It assesses attention, immediate memory, visuospatial/ construction, language, and delayed memory (Gold et al., 1999). Schizophrenics score significantly lower than normal subjects the decrement is correlated with diminished psychosocial status. Compared to placebo, the DMXB-A significantly improved overall performance and specifically improved function on the Attention subscale. Inhibition of the P50 response to repeated stimulus, the sensory gating measure that led to identification of nicotinic receptor deficits in schizophrenia, also improved (Olincy et al., 2006). 

Court J, Spurden D, Lloyd S, McKeith I, Ballard C, Cairns N. et al. 1999. Neuronal nicotinic receptors in dementia with Lewy bodies and schizophrenia Alpha-bungarotoxin and nicotine binding in the thalamus. J Neurochem 73 1590-1597. 

Freedman R, Hall M, Adler LE, Leonard S. 1995. Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia. Biol Psychiatry 38 22-33. 

Martin-Ruiz CM, et al. 2003. Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia. Biol Psychiatry 54 1222-1233. 

Marutle A, Zhang X, Court J, Piggot M, Johnson M, et al. 2001. Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia. J Chem Neuroanat 22 115-126. 

Sacco KA, Termine A, Seyal A, Dudas MM, Vessicchio JC, et al. 2005. Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia Involvement of nicotinic receptor mechanisms. Arch of Gen Psychiatry 62 649-659. 

Xu J, Pato MT, Dalla Torre C, Medeiros H, Carvalho C, et al. 2001. Evidence of linkage disequilibrium between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families. Am J Med Gen 105 669-674. 

George TP, Termine A, Sacco KA, Allen TM, Reutenauer E, et al. 2006. A preliminary study of the effects of cigarette smoking on prepulse inhibition in schizophrenia Involvement of nicotinic receptor mechanisms. Schizophr Res 87 307-315. 

De Luca V, Likhodi O, Van Tol HH, Kennedy JL, Wong AH. 2006. Regulation of alpha7-nicotinic receptor subunit and alpha7-like gene expression in the prefrontal cortex of patients with bipolar disorder and schizophrenia. Acta Psy-chiatr Scand 114 211-215. 

Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE. 1976. The effects of morphine- and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther 197 517-532. Martin-Ruiz CM, Haroutunian VH, Long P, Young AH, Davis KL, et al. 2003. Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia. Biol Psychiatry 54 1222-1233. 

Laminar distribution of nicotinic receptor subtypes in cortical regions in schizophrenia. J Chem Neuroanat 22 115-126. 

Adler LE, Olincy A, Waldo M, Harris JG, Griffith J, Stevens K, Flach. 1998. Schizophrenia, sensory gating, and nicotinic receptors. Schizophrenia Bulletin 24 189-202. 

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