David Baxter PhD
Late Founder
Nicotine increases GABA in schizophrenia, relieves symptoms
By Andrew Czyzewski
17 October 2008
Proc Natl Acad Sci USA 2008; Advance online publication
Scientists have uncovered the mechanism by which nicotine appears to alleviate some of the symptoms of schizophrenia and hope to develop more selective treatments based on this knowledge.
Many previous reports have found heavy smoking to be prevalent in the schizophrenia population, with patients often claiming the habit helps relieve symptoms such as hallucinations, A Guidotti (University of Illinois at Chicago, USA) and colleagues observe.
The major active component inhaled from cigarettes is nicotine, a potent cholinergic receptor agonist. Nicotine alters brain chemistry by increasing the function of glutamic acid decarboxylase (GAD)67, found at abnormally low levels in the brain of schizophrenia patients, although the exact mechanism is unclear.
Because detailed investigation of these processes can only be inferred from the postmortem brains of schizophrenia patients, the researchers turned their focus to a mouse model.
When mice were injected with nicotine (4.5?22 ?mol/kg, four injections during the 12-h light cycle for 4 days) there was increased frontal cortex expression of GAD67 and the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
The authors showed that nicotine increased GABA production by enhancing GAD67 in the upper two layers of the frontal cortex.
Pre-treating the mice with mecamylamine, a cholinergic receptor blocker that readily crosses the blood?brain barrier, curbed the nicotine-induced increase in GAD67 expression.
The researchers propose that nicotine, by acting on nicotinic acetylcholine receptors located on GABAergic neurons, increases the expression of GAD67, which may help to mitigate the hallucinations typical of schizophrenia that are thought to be associated with a deficit of GABAergic neurotransmission.
Guidotti and colleagues comment: ?Nicotinic agonists are one of several treatment options for schizophrenia currently under investigation.
?The use of synthetic ligands to selectively down-regulate GABAergic neurons may represent an innovative attempt to control the GAD67 and other gene promoters while leaving cells that do not express cholinergic receptor intact.?
The research is published in the Proceedings of the National Academy of Sciences of the USA.
By Andrew Czyzewski
17 October 2008
Proc Natl Acad Sci USA 2008; Advance online publication
Scientists have uncovered the mechanism by which nicotine appears to alleviate some of the symptoms of schizophrenia and hope to develop more selective treatments based on this knowledge.
Many previous reports have found heavy smoking to be prevalent in the schizophrenia population, with patients often claiming the habit helps relieve symptoms such as hallucinations, A Guidotti (University of Illinois at Chicago, USA) and colleagues observe.
The major active component inhaled from cigarettes is nicotine, a potent cholinergic receptor agonist. Nicotine alters brain chemistry by increasing the function of glutamic acid decarboxylase (GAD)67, found at abnormally low levels in the brain of schizophrenia patients, although the exact mechanism is unclear.
Because detailed investigation of these processes can only be inferred from the postmortem brains of schizophrenia patients, the researchers turned their focus to a mouse model.
When mice were injected with nicotine (4.5?22 ?mol/kg, four injections during the 12-h light cycle for 4 days) there was increased frontal cortex expression of GAD67 and the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
The authors showed that nicotine increased GABA production by enhancing GAD67 in the upper two layers of the frontal cortex.
Pre-treating the mice with mecamylamine, a cholinergic receptor blocker that readily crosses the blood?brain barrier, curbed the nicotine-induced increase in GAD67 expression.
The researchers propose that nicotine, by acting on nicotinic acetylcholine receptors located on GABAergic neurons, increases the expression of GAD67, which may help to mitigate the hallucinations typical of schizophrenia that are thought to be associated with a deficit of GABAergic neurotransmission.
Guidotti and colleagues comment: ?Nicotinic agonists are one of several treatment options for schizophrenia currently under investigation.
?The use of synthetic ligands to selectively down-regulate GABAergic neurons may represent an innovative attempt to control the GAD67 and other gene promoters while leaving cells that do not express cholinergic receptor intact.?
The research is published in the Proceedings of the National Academy of Sciences of the USA.
