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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been proposed that activation of nicotinic acetylcholine receptors (nAChRs) can activate the prefrontal cortex, enhancing attention and cognition. Nicotine can stimulate the release of several different neurotransmitters in many brain regions. In the present study, we found that stimulation of nAChRs by nicotine or the endogenous agonist, acetylcholine (ACh), induces a large spontaneous increase in glutamate release onto layer V pyramidal neurons of the prefrontal cortex. This release of glutamate, measured by spontaneous excitatory postsynaptic currents (sEPSCs) in the prefrontal cortical slice, depends on intact thalamocortical terminals. It can be suppressed by mu-opioids or eliminated by blocking action potentials. The increase in sEPSCs is sensitive to low concentrations of nicotine, suggesting the involvement of high-affinity (eg alpha(4)beta(2)) nAChRs. Recent work has shown alterations in prefrontal alpha(4)beta(2) nAChRs in autism and schizophrenia, two conditions that are distinguished by abnormal prefrontal cortical activation as well as difficulty in certain aspects of cognition and integrating social and emotional cues. We show that mice lacking the beta(2) nAChR subunit do not show increased sEPSCs with either nicotine or ACh, again implicating high-affinity nicotinic receptors. These findings give new insight into the mechanism by which nicotine affects excitatory neurotransmission to the output neurons of the cerebral cortex in a pathway that is critical for cognitive function and reward expectation.
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PMID:Nicotine induces glutamate release from thalamocortical terminals in prefrontal cortex. 1258 74

Nicotine enhances several cognitive and psychomotor behaviors, and nicotinic antagonists cause impairments in tasks requiring cognitive effort. To explore the contribution of nicotinic receptors to complex cognitive functions, we developed an automated method to investigate sequential locomotor behavior in the mouse and an analysis of social behavior. We show that, in the beta2-/- mutant, the high-order spatiotemporal organization of locomotor behavior, together with conflict resolution and social interaction, is selectively dissociated from low-level, more automatic motor behaviors. Such deficits in executive functions resemble the rigid and asocial behavior found in some psychopathological disorders such as autism and attention deficit hyperactivity disorder.
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PMID:Executive and social behaviors under nicotinic receptor regulation. 1287 1

Evidence supports the hypothesis that normalization of cholinergic tone by selective antagonism of neuronal nicotinic acetylcholine receptors (NNRs) may ameliorate the core symptoms of autism. As often is the case, epidemiology has provided the first important clues. It is well recognized that psychiatric patients are significantly more often smokers than the general population. The only known exceptions are obsessive-compulsive disorder (OCD), catatonic schizophrenia and interestingly, autism. In this regard, clinical studies with nicotine have demonstrated amelioration of symptoms of a number of diseases and disorders, including Alzheimer's disease, Parkinson's disease, ADHD and Tourette's syndrome. Nicotine's agonist properties at CNS NNRs have been implicated in these effects and support the concept of self-medication as a strong motivation for smoking in cognitively compromised individuals. On the other hand, the inverse correlation between autism and smoking suggests that smoking does not provide symptomatic relief and may actually be indicative of an active avoidance of nicotine's agonist effects in this disorder. Neuroanatomical evidence is consistent with this idea based on the presence of hypercholinergic architecture in the autistic brain, particularly during the first few years of development, making the avoidance of further stimulation of an already hyperactive cholinergic system plausible. This may also explain why stimulants (known to increase dopamine levels as do NNR agonists) appear to aggravate autistic symptoms and why studies with cholinesterase inhibitors that increase acetylcholine levels in the brain have yielded variable effects in autism. Taken together, the evidence suggests the possibility that nicotinic cholinergic antagonism may in fact be palliative. Pharmacological evidence supports this hypothesis. For example, antidepressants, many of which are now known to be non-competitive NNR antagonists, have been used successfully to treat a number of autistic symptoms. More specifically, there is anecdotal evidence from at least one medical practitioner that mecamylamine, a non-selective NNR antagonist, is effective in treating many autistic symptoms, particularly those that are refractory to most other treatments. Clearly there is a need for carefully controlled clinical studies with novel selective NNR antagonists to explore their potential as a new and exciting approach for the treatment of autism.
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PMID:Nicotinic cholinergic antagonists: a novel approach for the treatment of autism. 1640 87

Aggression remains a major cause of morbidity in patients with autism spectrum disorder (ASD). Current pharmacotherapy for aggression is not always effective and is often associated with morbidity. Nicotinic acetylcholinergic neurotransmission may play a prominent role in ASD pathophysiology based on human and animal studies, and preclinical studies show nicotine administration can reduce aggression-related behaviors. Transdermal nicotine has been used to treat agitation in neuropsychiatric conditions with cholinergic dysfunction. Here we report the use of transdermal nicotine as an adjunctive medication to treat aggression in a hospitalized adolescent with ASD. Nicotine patch was recurrently well tolerated, and reduced the need for emergency medication and restraint. These findings suggest further study of transdermal nicotine for aggression comorbid with ASD is warranted.
J Autism Dev Disord 2015 Sep
PMID:Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder. 2598 11