Nicotine abstinence in the mouse
96
Citation
25
Reference
10
Related Paper
Citation Trend
Keywords:
Mecamylamine
Nicotine withdrawal
Nicotinic acetylcholine receptors appear to be quite ancient phylogenetically and are used in the nervous systems of a great number of species across broad parts of the animal kingdom. They play important roles in a variety of neurobehavioral functions from neuromuscular activation to cognitive function. Nicotinic receptor function is an excellent field in which to assess the potential commonalities of neurobehavioral functions across animal species. Nicotinic receptors are remarkably consistent across species and the behavioral effects of nicotinic treatments have been very well determined in mammals. Since zebrafish are an emerging aquatic model for studying neurobehavioral function, we have determined the effects of nicotine, the prototypic nicotinic agonist as well as nicotinic antagonists on cognitive function, exploratory behavior and stress response in a series of behavioral tests we have developed to reliably index these behavioral functions. The overall hypothesis of this line of investigation was that nicotine would have similar behavioral effects in zebrafish as in mammals when analogous tests of behavioral function are used. As with mammalian species, nicotine significantly improves learning and memory at low to moderate doses in zebrafish with an inverted J-shaped dose-effect function. The nicotine-induced learning improvement in zebrafish is reversed with the nicotinic antagonist mecamylamine and is accompanied by increased brain dopamine metabolite levels, an effect which is also reversed with mecamylamine. Also, as in mammals, nicotine has anxiolytic effects in zebrafish. Nicotine significantly reduces bottom dwelling in the novel tank diving task. This effect is reversed by either α7 or α4β2 nicotinic antagonist coadministration. In many respects nicotine has similar effects in zebrafish as in rodents and humans. These studies point to the value of zebrafish as models of human neurobehavioral function.
Mecamylamine
Nicotinic Antagonist
Cite
Citations (1)
Mecamylamine
Cytisine
Methyllycaconitine
Nicotinic Antagonist
Epibatidine
Chlorisondamine
Cite
Citations (13)
Mecamylamine
Nicotinic Antagonist
Cite
Citations (57)
In an effort to investigate the nature of brain nicotinic receptors receptor binding studies have been undertaken using nicotinic radioligands. With 3H-nicotine or the 3H-azetidine analogue of nicotine the Scatchard plot yielded a high and lower affinity site; whereas, with 3H-methylcarbamylcholine (3H-MCC) only the lower affinity site was observed. Based on the observation that the addition of a methyl group on carbamylcholine yielded a potent and specific nicotinic agonist, a number of nicotinic agonists and antagonists have been synthesized and their structure-activity relationships described. Studies are described using 3H-mecamylamine as a ligand for investigating the ion channel associated with brain nicotinic receptors. A good correlation was observed between the Ki values of a variety of mecamylamine and pempidinge analogues and their ability to antagonize the psychotropic effects of nicotine. Since nicotine competed for 3H-mecamylamine binding, it was inferred that nicotine may be interacting with the ion channel as well as with the recognition site.
Mecamylamine
Cytisine
Nicotinic Antagonist
Cite
Citations (0)
Abstract The loss of central nicotinic receptors is a neurochemical hallmark of several degenerative brain disorders, notably Alzheimer's disease (AD) and Parkinson's disease (PD). However, uncertainty has remained about the significance of this loss for the cognitive symptomatology of these disorders. Symptoms of impaired acquisition of information and short‐term storage, impaired memory consolidation, attention, visual perception, and speed may reflect nicotinic lesions. Administration of the nicotinic antagonist mecamylamine in young and elderly humans produces significant dose‐related impairment of new learning, liberalization of response bias, and slowing of reaction time. These results suggest that mecamylamine may in part model the results of nicotinic receptor loss in AD and that nicotinic augmentation of some aspects of cognitive functioning may be a worthwhile strategy to pursue, particularly if agents can be developed that are more selective than nicotine itself. © 1994 Wiley‐Liss, Inc.
Mecamylamine
Nicotinic Antagonist
Neurochemical
Cite
Citations (18)
Mecamylamine
Chlorisondamine
Nicotinic Antagonist
Radial arm maze
Methyllycaconitine
Cite
Citations (21)
Mecamylamine
Neurochemical
Nicotinic Antagonist
Cite
Citations (135)
Mecamylamine
Nicotinic Antagonist
Ganglionic blocker
Epibatidine
Cytisine
Cite
Citations (13)
Mecamylamine
Cite
Citations (33)
Mecamylamine
Nicotine withdrawal
Physical dependence
Cite
Citations (59)