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Guest
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Recall that nitric oxide affects histone acetylation in the brain [PMID
19704855] and histone acetylation regulates long-term
potentiation/memory, as I've just posted. I'd assume NO elevates CREB
until proven otherwise. Perhaps OCD can be viewed as an extreme memory
formation event.
Nitric Oxide. 2009 Sep;21(2):140-7. Epub 2009 Jul 5.
Role of nitric oxide in obsessive-compulsive behavior and its
involvement in the anti-compulsive effect of paroxetine in mice.
Umathe SN, Bhutada PS, Jain NS, Mundhada YR, Borkar SS, Dhumal B.
Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj
Nagpur University, Mahatma Jyotibha Fuley Parisar, Nagpur 440 033, India.
In view of the reports that nitric oxide modulates the neurotransmitters
implicated in obsessive-compulsive disorder, patients with
obsessive-compulsive disorder exhibit higher plasma nitrate levels, and
drugs useful in obsessive-compulsive disorder influence nitric oxide, we
hypothesized that nitric oxide may have some role in
obsessive-compulsive behavior. We used marble-burying behavior of mice
as the animal model of obsessive-compulsive disorder, and nitric oxide
levels in brain homogenate were measured using amperometric nitric
oxide-selective sensor method. Intraperitoneal administration of nitric
oxide enhancers viz. nitric oxide precursor-l-arginine (800 mg/kg),
nitric oxide donor-sodium nitroprusside (3 mg/kg) or phosphodiesterase
type 5 inhibitor-sildenafil (3 mg/kg) significantly increased
marble-burying behavior as well as brain nitrites levels, whereas
treatment with 7-nitroindazole-neuronal nitric oxide synthase inhibitor
(20-40 mg/kg, i.p.) or paroxetine-selective serotonin reuptake inhibitor
(5-10 mg/kg, i.p.) dose dependently attenuated marble-burying behavior
and nitrites levels in brain. Further, co-administration of
sub-effective doses of 7-nitroindazole (10 mg/kg) and paroxetine (2.5
mg/kg) significantly attenuated marble-burying behavior. Moreover,
pretreatment with l-arginine (400 mg/kg, i.p.), sodium nitroprusside
(2.0 mg/kg, i.p.) or sildenafil (2.0 mg/kg, i.p.) significantly
attenuated the inhibitory influence of 7-nitroindazole (40 mg/kg) or
paroxetine (10 mg/kg) on marble-burying behavior as well as on brain
nitrites levels. None of the above treatment had any significant
influence on locomotor activity. In conclusion, obsessive compulsive
behavior in mice appears related to nitric oxide in brain, and
anti-compulsive effect of paroxetine appears to be related to decrease
central levels of nitric oxide.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 19584001 |
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