Adrenaline Key To Why Anti depressants Work???

[Guest guest]

June 02, 2004

Adrenaline Packs a Powerful Punch in the

Use of Antidepressants, According to an

Animal-Model Study at Penn

Adrenaline-Deficient Mice Lack Responses to Antidepressant Drugs

(Philadelphia, PA)—Researchers from the University of Pennsylvania

School of Medicine found that norepinephrine (adrenaline) plays an

important role in animals in determining behavioral effects in some

of the most commonly prescribed antidepressants, regardless of which

biochemical pathway the drug uses to alleviate symptoms of

depression. This finding -- published in the May 2004 Proceedings of

the National Academy of Sciences -- should help scientists design

more effective drugs for patients.

Using genetically-altered mice unable to produce norepinephrine,

they tested behavioral changes brought on by two different

antidepressant classes. With the exception of one drug, they found

that those lacking norepinephrine did not respond to the

drugs. " Millions of Americans suffer from major depressive disorders

and this study helps us understand how antidepressant drugs are

processed to produce clinical therapeutic effects. It helps us

understand how to redesign better drugs and which treatments will

work better for which patients, " says the study's lead author, Irwin

Lucki, PhD, Professor of Psychiatry and Pharmacology and Director of

the Behavioral Psychopharmacology Laboratory at Penn.

There are currently two major classes of antidepressants used to

treat depression: norepinephrine reuptake inhibitors (which work by

increasing the synaptic activty of adrenaline

in the brain); and selective serotonin reuptake inhibitors (which

elicit their effects by increasing the activity of serotnin in the

brain). Previously, it was believed that SSRIs – whose over-the-

counter names include Prozac, Zoloft, Paxil, and Celexia – produced

effects on the serotonergic system only; but the Penn researchers'

findings showed that the effects of most SSRIs can also depend on

responses from the noradrenergic system. " This study is the first to

use this unique animal model to test whether the drugs are still

effective in animals that lack norepinephrine, a key

neurotransmitter in the brain, " Lucki adds.

The researchers tested eight commonly prescribed antidepressant

drugs, including four SSRIs. The SSRI medications tested were

fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil) and

citalopram (Celexia). In animal models, those able to produce

norepinephrine experienced behavioral changes when given the

antidepressants. But all of the antidepressants, except citalopram,

failed to work in the models lacking norepinephrine. These results

provide striking evidence that norepinephrine plays a critical role

for the creation of desired behavioral effects of most classes of

antidepressant compounds including the SSRIs.

Penn researchers also contributing to this study include: F.

Cryan, Olivia F. O'Leary, Sung-Ha Jin, C. Friedland, Ming

Ouyang, Bradford R. Hirsch, E. Page, Ashutosh Dalvi, and

A. .

The study was funded by grants from the United States Public Health

Service, The National Institute of Mental Health, The National

Institute of Neurological Disorders and Stroke, and a Young

Investigator Award from the National Alliance for Research on

Schizophrenia and Depression.

http://www.uphs.upenn.edu/news/News_Releases/june04/Adrenaline.html

[Guest guest]

June 02, 2004

Adrenaline Packs a Powerful Punch in the

Use of Antidepressants, According to an

Animal-Model Study at Penn

Adrenaline-Deficient Mice Lack Responses to Antidepressant Drugs

(Philadelphia, PA)—Researchers from the University of Pennsylvania

School of Medicine found that norepinephrine (adrenaline) plays an

important role in animals in determining behavioral effects in some

of the most commonly prescribed antidepressants, regardless of which

biochemical pathway the drug uses to alleviate symptoms of

depression. This finding -- published in the May 2004 Proceedings of

the National Academy of Sciences -- should help scientists design

more effective drugs for patients.

Using genetically-altered mice unable to produce norepinephrine,

they tested behavioral changes brought on by two different

antidepressant classes. With the exception of one drug, they found

that those lacking norepinephrine did not respond to the

drugs. " Millions of Americans suffer from major depressive disorders

and this study helps us understand how antidepressant drugs are

processed to produce clinical therapeutic effects. It helps us

understand how to redesign better drugs and which treatments will

work better for which patients, " says the study's lead author, Irwin

Lucki, PhD, Professor of Psychiatry and Pharmacology and Director of

the Behavioral Psychopharmacology Laboratory at Penn.

There are currently two major classes of antidepressants used to

treat depression: norepinephrine reuptake inhibitors (which work by

increasing the synaptic activty of adrenaline

in the brain); and selective serotonin reuptake inhibitors (which

elicit their effects by increasing the activity of serotnin in the

brain). Previously, it was believed that SSRIs – whose over-the-

counter names include Prozac, Zoloft, Paxil, and Celexia – produced

effects on the serotonergic system only; but the Penn researchers'

findings showed that the effects of most SSRIs can also depend on

responses from the noradrenergic system. " This study is the first to

use this unique animal model to test whether the drugs are still

effective in animals that lack norepinephrine, a key

neurotransmitter in the brain, " Lucki adds.

The researchers tested eight commonly prescribed antidepressant

drugs, including four SSRIs. The SSRI medications tested were

fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil) and

citalopram (Celexia). In animal models, those able to produce

norepinephrine experienced behavioral changes when given the

antidepressants. But all of the antidepressants, except citalopram,

failed to work in the models lacking norepinephrine. These results

provide striking evidence that norepinephrine plays a critical role

for the creation of desired behavioral effects of most classes of

antidepressant compounds including the SSRIs.

Penn researchers also contributing to this study include: F.

Cryan, Olivia F. O'Leary, Sung-Ha Jin, C. Friedland, Ming

Ouyang, Bradford R. Hirsch, E. Page, Ashutosh Dalvi, and

A. .

The study was funded by grants from the United States Public Health

Service, The National Institute of Mental Health, The National

Institute of Neurological Disorders and Stroke, and a Young

Investigator Award from the National Alliance for Research on

Schizophrenia and Depression.

http://www.uphs.upenn.edu/news/News_Releases/june04/Adrenaline.html