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Recent News and Articles on the Keywords: schizophrenia + new + ketamine  Related to the article below (Last Update: 5/13/2008)


University of Manchester
Study shows how 'horse tranquiliser' stops depression
University of Manchester, UK - May 2, 2008
Ketamine, an anaesthetic that is popular with doctors on the battlefield and also with vets because it allows a degree of awareness without pain, is a new ...
Hippie dream, modern nightmare
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Ketamine and and crystal powder also saw price falls while the price of cocaine remained stable. The price of cannabis, however, rose over the same period. ...
Source: Google News

… amphetamine-induced striatal dopamine release by ketamine in humans: implications for schizophrenia -
LS Kegeles, A Abi-Dargham, Y Zea-Ponce, J … - Biological Psychiatry, 2000 - Elsevier
... dopamine release observed in schizophrenia might result ... Presbyterian Medical Center
and New York State ... to drugs of abuse potential (ketamine and amphetamine). ...

… Processing in Healthy Volunteers Implications for Models of Cognitive Deficits in Schizophrenia -
D Umbricht, L Schmid, R Koller, FX Vollenweider, D … - Archives of General Psychiatry, 2000 - Am Med Assoc
... the basis of neurocognitive deficits in schizophrenia are addressed ... in this window]
[in a new window]. Figure 1. Effects of ketamine administration on mismatch ...

… of Deficient Sensorimotor Gating to Study the Pathophysiology and New Treatments of Schizophrenia -
NR Swerdlow, MA Geyer - Schizophrenia Bulletin, 1998 - MPRC
... Furthermore, ketamine has been shown to reduce PPI in normal control subjects
(Karper et al. ... Pathophysiology and New Treatments of Schizophrenia ...

The N-methyl-d-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and … -
G Ellison - Brain Research Reviews, 1995 - Elsevier
... state is more pharmacologically similar to schizophrenia than was ... heat-shock proteins
produced by ketamine, dizocilpine and ... in birth rate of new granule ceils ...

… effects on the dopamine D 2 and serotonin 5-HT 2 receptors?implications for models of schizophrenia -
S Kapur, P Seeman - Molecular Psychiatry, 2002 - nature.com
... Abstract. Ketamine and PCP are commonly used as selective NMDA receptor antagonists
to model the putative hypoglutamate state of schizophrenia and to test new ...

Management of the Negative Symptoms of Schizophrenia: New Treatment Options. -
HJ M?ller - CNS Drugs, 2003 - cnsdrugs.adisonline.com
... dose-finding studies for the new compounds. ... in several brain regions in
schizophrenia.[173]The ... anaesthetics (such as phencyclidine and ketamine) reproduces ...

The effects of low dose ketamine on sensory gating, neuroendocrine secretion and behavior in healthy … -
BNM van Berckel, B Oranje, JM van Ree, MN Verbaten … - Psychopharmacology, 1998 - Springer
... processes further. Key words NMDA ? Ketamine ? Prepulse inhibition ?
P50 reduction ? Schizophrenia Introduction Patients with ...

The Effects of Small-Dose Ketamine on Propofol Sedation: Respiration, Postoperative Mood, Perception … -
RF Mortero, LD Clark, MM Tolan, RJ Metz, K Tsueda, … - Anesthesia & Analgesia, 2001 - IARS
... Neurotransmitter aberrations in schizophrenia: new perspectives and therapeutic
implications ... Propofol inhibits ketamine-induced expression in the rat posterior ...

… of Ketamine-Induced Thought Disorder in Healthy Volunteers and Thought Disorder in Schizophrenia -
CM Adler, AK Malhotra, I Elman, T Goldberg, M Egan … - American Journal of Psychiatry, 1999 - Am Psychiatric Assoc
... on the Scale for the Assessment of Thought, Language, and Communication for patients
with schizophrenia and healthy volunteers receiving ketamine did not ...

Clinical and sensorimotor gating effects of ketamine in normals. -
EJ Duncan, SH Madonick, A Parwani, B Angrist, R … - Neuropsychopharmacology, 2001 - ncbi.nlm.nih.gov
... and sensorimotor gating effects of ketamine in normals ... Health Care System/New York
Campus, New York, NY ... between PCP psychosis and schizophrenia have contributed ...

Source: Google Scholar

Knowing how ketamine impairs brain circuitry may lead to new therapies for schizophrenia

Scientists know that the drug ketamine – street name “Special K” – can induce schizophrenia-like symptoms in drug abusers. Ketamine is also used as an anesthetic and, more recently, as an antidepressant – raising concerns by researchers at the University of California, San Diego (UCSD) School of Medicine, who have found that ketamine leads to the impairments in brain circuitry observed in both drug abusers and schizophrenic patients by causing increased production of a toxic free radical called “superoxide.” Their findings, which could point the way to novel treatments for schizophrenia, will be published in the December 7 issue of the journal Science.

A research team led by Laura Dugan, M.D., Larry L. Hillblom Professor of Geriatrics and research scholar with the UCSD Stein Institute for Research on Aging, discovered an unexpected link between the inflammatory enzyme complex NADPH oxidase and the dysfunction of certain brain neurons exposed to ketamine. NADPH oxidase is normally found in white blood cells circulating outside the brain, where it helps kill bacterial and fungal infections by producing superoxide, a compound that can cause substantial damage to cells.

“Because of NADPH oxidase’s protective role in fighting infection, it was very surprising to find that the complex wears a second hat – it is also critical for modulating signaling in the brain,” said first author M. Margarita Behrens, Ph.D., Division of Geriatric Medicine, UCSD School of Medicine.

According to Behrens, it was known that ketamine initially impairs the inhibitory circuitry in the brain’s cortex and hippocampus by blocking the NMDA receptor, a molecule on the cell surface that controls the activity of neurons. But the UCSD researchers discovered that, as a result of blocking the receptor, ketamine also substantially increased the activity of NADPH oxidase, causing further disruption of neuronal signaling.

“Ketamine causes a ‘disinhibition’ of brain circuitry, taking the brakes off the system and causing overexcitation of the brain in response to a stimulus,” said Behrens. “This overexcitation activates NADPH oxidase, which then produces superoxide – resulting in detrimental changes in key synaptic proteins and profoundly affecting nervous system function.”

The result is impairment of the brain circuitry involved in memory, attention and other key functions related to learning. Loss of such functions sets up individuals for psychosis and deficits in information processing, resulting in symptoms such as hallucinations and delusions, as well as social withdrawal and cognitive problems, according to Behrens.

Using ketamine, Behrens and Dugan mimicked features of schizophrenia in mice, and then analyzed neurons in a region of the mouse brain that corresponds to the prefrontal cortex in humans where profound changes occur in patients with schizophrenia. The researchers found a substantial increase in the activity of NADPH oxidase, and that this activity made some neurons in this inhibitory circuitry “disappear.” When the researchers blocked the activity of NADPH oxidase with an inhibitor, or with a compound that annihilates superoxide, these neurons were protected.

“Our findings suggest that compounds that inhibit NADPH oxidase in the brain, without totally blocking its protective function of killing bacteria, could provide future therapies for schizophrenia or other diseases in humans that exhibit similar changes in neural circuitry,” said Behrens.

###

Additional contributors to the paper include Sameh S. Ali, Diep N. Dao, Jacinta Lucero, Grigoriy Shekhtman and Kevin L. Quick, Department of Medicine, UCSD Division of Geriatric Medicine. The research was funded in part by the Larry L. Hillblom Endowment and NARSAD.
 
 
 
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