INT149467

Context Info Confidence 0.55 First Reported 2008 Last Reported 2011 Negated 0 Speculated 0 Reported most in Body Documents 2 Total Number 6 Disease Relevance 4.73 Pain Relevance 1.16

signal transduction (Avpr1b) plasma membrane (Avpr1b) response to stress (Avpr1b) signal transducer activity (Avpr1b)

Anatomy Link Frequency plasma 1 Avpr1b (Mus musculus)

Pain Link Frequency Relevance Heat Desipramine 2 99.40 fluoxetine 5 99.08 Neuropeptide 1 92.96 tricyclic antidepressant 3 89.08 sSRI 3 87.84 depression 41 86.56 antagonist 85 83.76 antidepressant 8 75.00 Serotonin 5 72.68 agonist 45 52.40

Disease Link Frequency Relevance Heat Targeted Disruption 305 99.96 Stress 402 96.04 Anxiety Disorder 40 87.84 Depression 51 86.56 Attention Deficit Hyperactivity Disorder 10 85.72 Aggression 85 57.84 Sprains And Strains 60 36.92 Overactive Bladder 5 24.24 Neurogenic Diabetes Insipidus 5 22.40 Obesity 15 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

As shown in Table II, we find some acute and chronic stressors are not influenced by the loss of the Avpr1b (e.g. acute severe restraint), some have a reduced ACTH response only (e.g. acute forced swimming stress) and some have both a reduced ACTH and CORT response in Avpr1b KOs compared to wild types (e.g. acute and repeated novel environment stress).

Negative_regulation (loss) of Avpr1b associated with stress

1) Confidence 0.55 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.76 Pain Relevance 0.04

We cannot totally rule out the possibility that mechanisms compensating for the loss of Avpr1b are active in the Avpr1b KO.

Negative_regulation (loss) of Avpr1b associated with targeted disruption

2) Confidence 0.55 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.61 Pain Relevance 0

As far as HPA axis function is concerned, clearly Crh (or Oxt) does not compensate for the loss of the Avpr1b in Avpr1b KO mice.

Negative_regulation (loss) of Avpr1b associated with targeted disruption

3) Confidence 0.55 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 1.37 Pain Relevance 0.04

Nevertheless, stress-induced ACTH levels in our Avpr1b KOs are consistently lower (often to basal levels) than wild-type controls, confirming any compensation (e.g. from the action of Crh) is not sufficient to fully counteract the loss of the Avpr1b (Lolait et al. 2007a,b; Stewart et al. 2008a,b).

Negative_regulation (loss) of Avpr1b associated with stress

4) Confidence 0.41 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.55 Pain Relevance 0.03

Fluoxetine and desipramine administration significantly attenuated plasma ACTH and CORT levels in male and female Avpr1b KO mice when compared to their wild-type counterparts.

Negative_regulation (attenuated) of Avpr1b in plasma associated with targeted disruption, desipramine and fluoxetine

5) Confidence 0.40 Published 2008 Journal Psychoneuroendocrinology Section Abstract Doc Link 18243568 Disease Relevance 0.65 Pain Relevance 0.95

Prepulse inhibition of the startle reflex is attenuated in Avpr1b KO mice (Egashira et al. 2005) suggesting that this mouse may be a suitable model to investigate sensorimotor gating.

Negative_regulation (attenuated) of Avpr1b associated with targeted disruption

6) Confidence 0.35 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.79 Pain Relevance 0.10

General Comments

This test has worked.