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Isabelle M. Maisonneuve - One of the best experts on this subject based on the ideXlab platform.
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brain regions mediating α3β4 Nicotinic Antagonist effects of 18 mc on nicotine self administration
European Journal of Pharmacology, 2011Co-Authors: Stanley D. Glick, Elizabeth M Sell, Sarah E Mccallum, Isabelle M. MaisonneuveAbstract:18-Methoxycoronaridine (18-MC), a putative anti-addictive agent, has been shown to decrease the self-administration of several drugs of abuse in rats. 18-MC is a potent Antagonist at α3β4 Nicotinic receptors. Consistent with high densities of α3β4 Nicotinic receptors being located in the medial habenula and the interpeduncular nucleus, 18-MC has been shown to act in these regions to decrease both morphine and methamphetamine self-administration. The present study was conducted to determine if 18-MC's effect on nicotine self-administration is mediated by acting in these same brain regions. Because moderate densities of α3β4 receptors occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, these brain areas were also examined as potential sites of action of 18-MC. Local administration of 18-MC into either the medial habenula, the basolateral amygdala or the dorsolateral tegmentum decreased nicotine self-administration. Surprisingly, local administration of 18-MC into the interpeduncular nucleus increased nicotine self-administration while local administration of 18-MC into the ventral tegmental area had no effect on nicotine self-administration. Similar effects were produced by local administration of either mecamylamine or conotoxin AuIB. These data are consistent with the hypothesis that 18-MC decreases nicotine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of α3β4 Nicotinic receptors in the medial habenula, basolateral amygdala, and dorsolateral tegmentum. The data also suggest that an action of 18-MC in the interpeduncular nucleus may attenuate aversive and/or depressive effects of nicotine.
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Brain regions mediating α3β4 Nicotinic Antagonist effects of 18-MC on methamphetamine and sucrose self-administration
European Journal of Pharmacology, 2008Co-Authors: Elizabeth M Sell, Isabelle M. MaisonneuveAbstract:The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the self-administration of several drugs of abuse. Previous work has established that 18-MC is a potent Antagonist at α3β4 Nicotinic receptors. Because high densities of α3β4 Nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine self-administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine self-administration. Similar results were produced by local administration into the same brain areas of two other α3β4 Nicotinic Antagonists, mecamylamine and α-conotoxin AuIB. Local administration of 18-MC, or the other Antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine self-administration. In contrast, local administration of 18-MC and the other Antagonists decreased sucrose self-administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of α3β4 Nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving α3β4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose self-administration.
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Brain regions mediating alpha3beta4 Nicotinic Antagonist effects of 18-MC on methamphetamine and sucrose self-administration.
European journal of pharmacology, 2008Co-Authors: Elizabeth M Sell, Isabelle M. MaisonneuveAbstract:The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the self-administration of several drugs of abuse. Previous work has established that 18-MC is a potent Antagonist at alpha3beta4 Nicotinic receptors. Because high densities of alpha3beta4 Nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine self-administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine self-administration. Similar results were produced by local administration into the same brain areas of two other alpha3beta4 Nicotinic Antagonists, mecamylamine and alpha-conotoxin AuIB. Local administration of 18-MC, or the other Antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine self-administration. In contrast, local administration of 18-MC and the other Antagonists decreased sucrose self-administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of alpha3beta4 Nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving alpha3beta4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose self-administration.
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18-MC reduces methamphetamine and nicotine self-administration in rats.
Neuroreport, 2000Co-Authors: Isabelle M. Maisonneuve, H A. DickinsonAbstract:In previous studies, 18-methoxycoronaridine (18-MC), a novel iboga alkaloid congener, has been found to decrease the intravenous self-administration of morphine and cocaine in rats. In the present study, 18-MC (1-40 mg/kg, i.p.) dose-dependently decreased the i.v. self-administration of methamphetamine and nicotine. As in the previous studies, drug self-administration was reduced for > or = 24 h after the highest dose of 18-MC. A comparison of 18-MC's interactions with all four drugs of abuse studied so far indicated that 18-MC is least effective in decreasing methamphetamine self-administration and most potent in decreasing nicotine self-administration. The results suggest that a Nicotinic Antagonist action of 18-MC contributes to its putative anti-addictive efficacy.
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An oral self-administration model of nicotine preference in rats: effects of mecamylamine.
Psychopharmacology, 1996Co-Authors: Stanley D. Glick, Kathleen E. Visker, Isabelle M. MaisonneuveAbstract:A new oral model of nicotine self-administration in rats has been described. The model utilizes a two-lever operant procedure with rats having a choice between nicotine and water reinforcement. Most (16 of 20) rats exhibited reliable preferences for nicotine solutions equal to or less than 32 μg/ml; preferences were inversely related to the concentration of nicotine. Mecamylamine (0.25–5.0 mg/kg), a Nicotinic Antagonist, reduced preferences for a low nicotine concentration (4 μg/ml) and enhanced preferences for a high nicotine concentration (32 μg/ml). The relationship of nicotine concentration to nicotine preference appeared to be consistent with previous reports of nicotine self-administration using the intravenous route in rats as well as the respiratory route (i.e., smoking) in humans. The mecamylamine-induced changes in nicotine preference were consistent with its Nicotinic Antagonist action as well as with effects of mecamylamine reported in humans. This model should be useful in the preclinical assessment of new agents as potential therapies in smoking cessation programs.
Edward D. Levin - One of the best experts on this subject based on the ideXlab platform.
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Decreasing Nicotinic receptor activity and the spatial learning impairment caused by the NMDA glutamate Antagonist dizocilpine in rats.
European Journal of Pharmacology, 2014Co-Authors: Dennis A. Burke, Pooneh Heshmati, Ehsan Kholdebarin, Edward D. LevinAbstract:Abstract Nicotinic systems have been shown by a variety of studies to be involved in cognitive function. Nicotinic receptors have an inherent property to become desensitized after activation. The relative role of Nicotinic receptor activation vs. net receptor inactivation by desensitization in the cognitive effects of Nicotinic drugs remains to be fully understood. In these studies, we tested the effects of the α7 Nicotinic receptor Antagonist methyllycaconitine (MLA), the α4β2 Nicotinic receptor Antagonist dihydro-β-erythroidine (DHβE), the nonspecific Nicotinic channel blocker mecamylamine and the α4β2 Nicotinic receptor desensitizing agent sazetidine-A on learning in a repeated acquisition test. Adult female Sprague–Dawley rats were trained on a repeated acquisition learning procedure in an 8-arm radial maze. MLA (1–4 mg/kg), DHβE (1–4 mg/kg), mecamylamine (0.125–0.5 mg/kg) or sazetidine-A (1 and 3 mg/kg) were administered in four different studies either alone or together with the NMDA glutamate Antagonist dizocilpine (0.05 and 0.10 mg/kg). MLA significantly counteracted the learning impairment caused by dizocilpine. The overall choice accuracy impairment caused by dizocilpine was significantly attenuated by co-administration of DHβE. Low doses of the non-specific Nicotinic Antagonist mecamylamine also reduced dizocilpine-induced repeated acquisition impairment. Sazetidine-A reversed the accuracy impairment caused by dizocilpine. These studies provide evidence that a net decrease in Nicotinic receptor activity can improve learning by attenuating learning impairment induced by NMDA glutamate blockade. This adds to evidence in cognitive tests that Nicotinic Antagonists can improve cognitive function. Further research characterizing the efficacy and mechanisms underlying Nicotinic Antagonist and desensitization induced cognitive improvement is warranted.
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Effects of AZD3480, a neuronal Nicotinic acetylcholine receptor agonist, and donepezil on dizocilpine-induced attentional impairment in rats.
Psychopharmacology, 2012Co-Authors: Amir H Rezvani, Marty Cauley, Edwin C. Johnson, Gregory J. Gatto, Edward D. LevinAbstract:Background and rationale Nicotinic acetylcholine systems play major roles in cognitive function. Nicotine and a variety of Nicotinic agonists improve attention, and Nicotinic Antagonist exposure impairs it. This study was conducted to investigate the effect of a novel Nicotinic receptor agonist at α4β2 Nicotinic receptors (AZD3480) on attention and reversal of pharmacologically induced attentional impairment produced by the NMDA glutamate Antagonist dizocilpine (MK-801).
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Nicotine effects on learning in zebrafish: the role of dopaminergic systems.
Psychopharmacology, 2008Co-Authors: Donnie Eddins, Ann Petro, Paul Williams, Daniel T Cerutti, Edward D. LevinAbstract:Nicotine improves cognitive function in a number of animal models including rats, mice, monkeys, and recently, zebrafish. The zebrafish model allows higher throughput and ease in discovering mechanisms of cognitive improvement. To further characterize the neural bases of nicotine effects on learning in zebrafish, we determined changes in dopaminergic systems that accompany nicotine-enhanced learning. Nicotine improved learning and increased brain levels of dihydroxyphenylacetic acid (DOPAC), the primary dopamine metabolite. There was a significant correlation between choice accuracy and DOPAC levels. The Nicotinic Antagonist mecamylamine blocked the nicotine-induced increase in DOPAC concentrations, in line with our previous finding that mecamylamine reversed nicotine-induced learning improvement. Dopamine systems are related to learning in zebrafish; nicotine exposure increases both learning rates and DOPAC levels; and Nicotinic Antagonist administration blocks nicotine-induced rises in DOPAC concentrations. Rapid cognitive assessment of drugs with zebrafish could serve as a useful screening tool for the development of new therapeutics for cognitive dysfunction.
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low dose mecamylamine improves learning of rats in the radial arm maze repeated acquisition procedure
Neurobiology of Learning and Memory, 2006Co-Authors: Edward D. Levin, Patrick D CaldwellAbstract:The Nicotinic Antagonist mecamylamine has been widely shown to cause cognitive impairment. However, these effects are mainly seen with high doses. There have been scattered findings that low doses of mecamylamine can have the opposite effect. This may be due to opposite effects of low doses of mecamylamine. In the current study, an extensive dose–effect function of mecamylamine was characterized in the low-dose range. Adult female Sprague–Dawley rats were trained on a repeated acquisition procedure on an automated 8-arm radial maze. Three of the eight arms were designated as correct for any particular session. Five trials per session were run. The number of errors per trial to find the three correct arms was determined. The rats were trained on the repeated acquisition procedure for at least 18 sessions at which time they showed reliable learning each session. Then, the effect of low doses of mecamylamine between 0 and 1 mg/kg were assessed in a repeated measures counterbalanced design. This dose range of mecamylamine did not affect performance on the first trial when the rats were naive to the array to be learned. On trials 2–5 a significant (p < .025) quadratic dose–effect function was seen over this dose range. The most substantial effect was seen with 0.125 mg/kg of mecamylamine, which caused a significant (p < .05) improvement relative to the saline control condition. The effect diminished with increasing mecamylamine doses and with the 1 mg/kg dose choice accuracy was back to control levels. This study showed that low doses of mecamylamine can effectively improve learning. A U-shaped dose–effect curve was documented. This suggests possible low-dose Nicotinic Antagonist lines of treatment for cognitive impairment.
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The Nicotinic Antagonist mecamylamine preferentially inhibits cocaine vs. food self-administration in rats
Physiology & Behavior, 2000Co-Authors: Edward D. Levin, Amir H Rezvani, Tonya Mead, Jed E. Rose, Camille Gallivan, Rita GrossAbstract:Abstract Nicotinic acetylcholine systems play important roles in addiction, and Nicotinic receptor stimulation stimulates dopamine release while the Nicotinic Antagonist mecamylamine reduces it. Reid et al. [Neuropsychopharmacology 20 (1999) 297.] recently found in human cocaine addicts that mecamylamine reduced cue-elicited cocaine craving. The current study assessed the impact of mecamylamine on cocaine self-administration in rats. Female Sprague–Dawley rats ( N =7) were implanted with intravenous (iv) catheters and trained to lever press for cocaine (0.32 mg/kg/infusion FR-1 with a 60-s timeout) in 45-min sessions. After 2 weeks of training, the rats were injected with saline or mecamylamine (1, 2, or 4 mg/kg sc) 10 min before the session. They received the same dose for 1 week with 1 week of uninjected testing between doses. Mecamylamine, compared to saline, significantly ( P N =8) were trained to lever press for food reinforcement. In these rats, the 1 and 2-mg/kg mecamylamine doses had no effect on food self-administration. Significant reductions in food self-administration were not seen unless the high dose of 4-mg/kg mecamylamine was used. Nicotinic Antagonist treatment reduces cocaine self-administration in rats at doses that do not cause generalized effects on food-reinforced responding. Nicotinic Antagonistic treatment may be a useful new approach to treat cocaine addiction.
Christopher M De Fiebre - One of the best experts on this subject based on the ideXlab platform.
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The alpha7 Nicotinic acetylcholine receptor-selective Antagonist, methyllycaconitine, partially protects against beta-amyloid1-42 toxicity in primary neuron-enriched cultures.
Brain research, 2004Co-Authors: Shelley E Martin, Nancy Ellen C De Fiebre, Christopher M De FiebreAbstract:Studies have suggested that the neuroprotective actions of alpha7 Nicotinic agonists arise from activation of receptors and not from the extensive desensitization which rapidly follows activation. Here, we report that the alpha7-selective Nicotinic Antagonist, methyllycaconitine (MLA), protects against beta-amyloid-induced neurotoxicity; whereas the alpha4beta2-selective Antagonist, dihydro-beta-erythroidine, does not. These findings suggest that neuroprotective actions of alpha7-acting agents arise from receptor inhibition/desensitization and that alpha7 Antagonists may be useful neuroprotective agents.
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the α7 Nicotinic acetylcholine receptor selective Antagonist methyllycaconitine partially protects against β amyloid1 42 toxicity in primary neuron enriched cultures
Brain Research, 2004Co-Authors: Shelley E Martin, Nancy Ellen C De Fiebre, Christopher M De FiebreAbstract:Studies have suggested that the neuroprotective actions of alpha7 Nicotinic agonists arise from activation of receptors and not from the extensive desensitization which rapidly follows activation. Here, we report that the alpha7-selective Nicotinic Antagonist, methyllycaconitine (MLA), protects against beta-amyloid-induced neurotoxicity; whereas the alpha4beta2-selective Antagonist, dihydro-beta-erythroidine, does not. These findings suggest that neuroprotective actions of alpha7-acting agents arise from receptor inhibition/desensitization and that alpha7 Antagonists may be useful neuroprotective agents.
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The α7 Nicotinic acetylcholine receptor-selective Antagonist, methyllycaconitine, partially protects against β-amyloid1–42 toxicity in primary neuron-enriched cultures
Brain Research, 2004Co-Authors: Shelley E Martin, Nancy Ellen C De Fiebre, Christopher M De FiebreAbstract:Studies have suggested that the neuroprotective actions of alpha7 Nicotinic agonists arise from activation of receptors and not from the extensive desensitization which rapidly follows activation. Here, we report that the alpha7-selective Nicotinic Antagonist, methyllycaconitine (MLA), protects against beta-amyloid-induced neurotoxicity; whereas the alpha4beta2-selective Antagonist, dihydro-beta-erythroidine, does not. These findings suggest that neuroprotective actions of alpha7-acting agents arise from receptor inhibition/desensitization and that alpha7 Antagonists may be useful neuroprotective agents.
Elizabeth M Sell - One of the best experts on this subject based on the ideXlab platform.
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brain regions mediating α3β4 Nicotinic Antagonist effects of 18 mc on nicotine self administration
European Journal of Pharmacology, 2011Co-Authors: Stanley D. Glick, Elizabeth M Sell, Sarah E Mccallum, Isabelle M. MaisonneuveAbstract:18-Methoxycoronaridine (18-MC), a putative anti-addictive agent, has been shown to decrease the self-administration of several drugs of abuse in rats. 18-MC is a potent Antagonist at α3β4 Nicotinic receptors. Consistent with high densities of α3β4 Nicotinic receptors being located in the medial habenula and the interpeduncular nucleus, 18-MC has been shown to act in these regions to decrease both morphine and methamphetamine self-administration. The present study was conducted to determine if 18-MC's effect on nicotine self-administration is mediated by acting in these same brain regions. Because moderate densities of α3β4 receptors occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, these brain areas were also examined as potential sites of action of 18-MC. Local administration of 18-MC into either the medial habenula, the basolateral amygdala or the dorsolateral tegmentum decreased nicotine self-administration. Surprisingly, local administration of 18-MC into the interpeduncular nucleus increased nicotine self-administration while local administration of 18-MC into the ventral tegmental area had no effect on nicotine self-administration. Similar effects were produced by local administration of either mecamylamine or conotoxin AuIB. These data are consistent with the hypothesis that 18-MC decreases nicotine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of α3β4 Nicotinic receptors in the medial habenula, basolateral amygdala, and dorsolateral tegmentum. The data also suggest that an action of 18-MC in the interpeduncular nucleus may attenuate aversive and/or depressive effects of nicotine.
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Brain regions mediating α3β4 Nicotinic Antagonist effects of 18-MC on methamphetamine and sucrose self-administration
European Journal of Pharmacology, 2008Co-Authors: Elizabeth M Sell, Isabelle M. MaisonneuveAbstract:The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the self-administration of several drugs of abuse. Previous work has established that 18-MC is a potent Antagonist at α3β4 Nicotinic receptors. Because high densities of α3β4 Nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine self-administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine self-administration. Similar results were produced by local administration into the same brain areas of two other α3β4 Nicotinic Antagonists, mecamylamine and α-conotoxin AuIB. Local administration of 18-MC, or the other Antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine self-administration. In contrast, local administration of 18-MC and the other Antagonists decreased sucrose self-administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of α3β4 Nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving α3β4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose self-administration.
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Brain regions mediating alpha3beta4 Nicotinic Antagonist effects of 18-MC on methamphetamine and sucrose self-administration.
European journal of pharmacology, 2008Co-Authors: Elizabeth M Sell, Isabelle M. MaisonneuveAbstract:The novel iboga alkaloid congener 18-methoxycoronaridine (18-MC) is a putative anti-addictive agent that has been shown, in rats, to decrease the self-administration of several drugs of abuse. Previous work has established that 18-MC is a potent Antagonist at alpha3beta4 Nicotinic receptors. Because high densities of alpha3beta4 Nicotinic receptors occur in the medial habenula and the interpeduncular nucleus and moderate densities occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, the present study was conducted to determine if 18-MC could act in these brain areas to modulate methamphetamine self-administration in rats. Local administration of 18-MC into either the medial habenula, the interpeduncular area or the basolateral amygdala decreased methamphetamine self-administration. Similar results were produced by local administration into the same brain areas of two other alpha3beta4 Nicotinic Antagonists, mecamylamine and alpha-conotoxin AuIB. Local administration of 18-MC, or the other Antagonists, into the dorsolateral tegmentum or the ventral tegmental area had no effect on methamphetamine self-administration. In contrast, local administration of 18-MC and the other Antagonists decreased sucrose self-administration when administered into the dorsolateral tegmentum or basolateral amygdala but had no effect when infused into the medial habenula, interpeduncular nucleus, or ventral tegmental area. These data are consistent with the hypothesis that 18-MC decreases methamphetamine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of alpha3beta4 Nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala. The data also suggest that the basolateral amygdala along with a different pathway involving alpha3beta4 receptors in the dorsolateral tegmentum mediate the effect of 18-MC on sucrose self-administration.
Tony P George - One of the best experts on this subject based on the ideXlab platform.
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Nicotinic Antagonist augmentation of selective serotonin reuptake inhibitor refractory major depressive disorder a preliminary study
Journal of Clinical Psychopharmacology, 2008Co-Authors: Tony P George, Kristi A Sacco, Jennifer C Vessicchio, Andrea H Weinberger, Douglas R ShytleAbstract:Background:There is evidence for Nicotinic hypercholinergic mechanisms in depression. Clinical relationships between tobacco use and depression suggest important effects of nicotine in major depressive disorder (MDD). It has been hypothesized that cigarette smoking may exert antidepressant effects,
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Neuropsychological deficits in nonsmokers with schizophrenia: effects of a Nicotinic Antagonist.
Schizophrenia Research, 2006Co-Authors: Kristi A Sacco, Angelo Termine, Melissa M Dudas, Aisha A Seyal, Taryn M Allen, Jennifer C Vessicchio, Bruce E Wexler, Tony P GeorgeAbstract:Abstract Background Biochemical, physiological and genetic evidence suggests dysregulation of central Nicotinic acetylcholine receptor (nAChR) systems in schizophrenia, which may contribute to neuropsychological dysfunction and the high rates of smoking in this disorder. To evaluate the effects of nAChR blockade on neuropsychological performance in schizophrenia without the confounding effects of cigarette smoking, we compared neuropsychological performance in schizophrenia and healthy control nonsmokers after pre-treatment with the centrally-acting nAChR Antagonist mecamylamine (MEC). Methods Using a within-subjects, counterbalanced design, schizophrenia ( n = 14) and control ( n = 15) nonsmokers were pre-treated for 3 days with MEC (0.0, 5.0, and 10.0 mg/day). Subjects performed repeated neuropsychological assessments including visuospatial working memory (VSWM), Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), Word Serial Position Test (WSPT) and Stroop Color Word Test (SCWT) during three sequential test sessions per week over three test weeks. Results We found significant main effects of schizophrenia diagnosis on: VSWM 30 and 60 delays ( p 's p p p Conclusions Our results suggest that there are a broad range of neuropsychological deficits in nonsmokers with schizophrenia. Furthermore, pretreatment with a centrally-acting nAChR Antagonist did not alter neuropsychological performance in either nonsmoking patients with schizophrenia or controls.
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Neuropsychological deficits in nonsmokers with schizophrenia: effects of a Nicotinic Antagonist.
Schizophrenia research, 2006Co-Authors: Kristi A Sacco, Angelo Termine, Melissa M Dudas, Aisha A Seyal, Taryn M Allen, Jennifer C Vessicchio, Bruce E Wexler, Tony P GeorgeAbstract:Biochemical, physiological and genetic evidence suggests dysregulation of central Nicotinic acetylcholine receptor (nAChR) systems in schizophrenia, which may contribute to neuropsychological dysfunction and the high rates of smoking in this disorder. To evaluate the effects of nAChR blockade on neuropsychological performance in schizophrenia without the confounding effects of cigarette smoking, we compared neuropsychological performance in schizophrenia and healthy control nonsmokers after pre-treatment with the centrally-acting nAChR Antagonist mecamylamine (MEC). Using a within-subjects, counterbalanced design, schizophrenia (n = 14) and control (n = 15) nonsmokers were pre-treated for 3 days with MEC (0.0, 5.0, and 10.0 mg/day). Subjects performed repeated neuropsychological assessments including visuospatial working memory (VSWM), Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), Word Serial Position Test (WSPT) and Stroop Color Word Test (SCWT) during three sequential test sessions per week over three test weeks. We found significant main effects of schizophrenia diagnosis on: VSWM 30 and 60 delays (p's < 0.01), CPT (% Hit Rate, Reaction Time, Variability Index; p < 0.01 for all outcomes), WCST (p < 0.01 for all outcomes) and Word Serial Position Test (p < 0.01). However, there were no main effects of repeated test administration (Session) or MEC dose on any of these outcomes, and no significant 3-way (DiagnosisxSessionxMEC dose) interactions. Our results suggest that there are a broad range of neuropsychological deficits in nonsmokers with schizophrenia. Furthermore, pretreatment with a centrally-acting nAChR Antagonist did not alter neuropsychological performance in either nonsmoking patients with schizophrenia or controls.
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Neuropsychological deficits in nonsmokers with schizophrenia: effects of a Nicotinic Antagonist.
Schizophrenia research, 2006Co-Authors: Kristi A Sacco, Angelo Termine, Melissa M Dudas, Aisha A Seyal, Taryn M Allen, Jennifer C Vessicchio, Bruce E Wexler, Tony P GeorgeAbstract:Biochemical, physiological and genetic evidence suggests dysregulation of central Nicotinic acetylcholine receptor (nAChR) systems in schizophrenia, which may contribute to neuropsychological dysfunction and the high rates of smoking in this disorder. To evaluate the effects of nAChR blockade on neuropsychological performance in schizophrenia without the confounding effects of cigarette smoking, we compared neuropsychological performance in schizophrenia and healthy control nonsmokers after pre-treatment with the centrally-acting nAChR Antagonist mecamylamine (MEC). Using a within-subjects, counterbalanced design, schizophrenia (n = 14) and control (n = 15) nonsmokers were pre-treated for 3 days with MEC (0.0, 5.0, and 10.0 mg/day). Subjects performed repeated neuropsychological assessments including visuospatial working memory (VSWM), Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), Word Serial Position Test (WSPT) and Stroop Color Word Test (SCWT) during three sequential test sessions per week over three test weeks. We found significant main effects of schizophrenia diagnosis on: VSWM 30 and 60 delays (p's < 0.01), CPT (% Hit Rate, Reaction Time, Variability Index; p < 0.01 for all outcomes), WCST (p < 0.01 for all outcomes) and Word Serial Position Test (p < 0.01). However, there were no main effects of repeated test administration (Session) or MEC dose on any of these outcomes, and no significant 3-way (DiagnosisxSessionxMEC dose) interactions. Our results suggest that there are a broad range of neuropsychological deficits in nonsmokers with schizophrenia. Furthermore, pretreatment with a centrally-acting nAChR Antagonist did not alter neuropsychological performance in either nonsmoking patients with schizophrenia or controls.
