JOURNAL ARTICLE

Regional patterns of compensation following genetic deletion of either 5-hydroxytryptamine(1A) or 5-hydroxytryptamine(1B) receptor in the mouse

D A Knobelman, R Hen, J A Blendy, I Lucki
Journal of Pharmacology and Experimental Therapeutics 2001, 298 (3): 1092-100
11504806
Plasticity in serotonergic transmission in serotonin or 5-hydroxytryptamine (5-HT) receptor mutants was examined by measuring the regulation of extracellular 5-HT levels in the striatum and ventral hippocampus of 5-HT(1A) and 5-HT(1B) receptor knockout mice using in vivo microdialysis. The efficacy of genetic deletion was verified by showing blunted regulation of extracellular 5-HT with selective 5-HT receptor agonists. 5-HT(1A) receptor knockout mice failed to demonstrate reduction of extracellular 5-HT in response to systemic administration of the 5-HT(1A) receptor agonist R-8-hydroxydipropylaminotetralin (R-8-OH-DPAT) and 5-HT(1B) receptor knockout mice failed to demonstrate reduction of extracellular 5-HT in response to systemic administration of the 5-HT(1B) receptor agonist CP 94,253. Plasticity also developed to deletion of the complementary autoreceptor. 5-HT(1A) receptor knockout mice demonstrated a significantly greater response to CP 94,253 in the striatum, but not the ventral hippocampus, suggesting the development of enhanced sensitivity of striatal 5-HT(1B) receptors. In 5-HT(1B) receptor knockout mice, R-8-OH-DPAT evoked a significantly diminished response in the ventral hippocampus, but not the striatum, suggesting the potential desensitization of 5-HT(1A) receptors in the median raphe nucleus. The pattern of regional compensations between somatodendritic and terminal autoreceptors was confirmed by pharmacological challenges using the selective serotonin reuptake inhibitor fluoxetine combined with either a 5-HT(1A) (WAY 100635) or a 5-HT(1B/1D) (GR 127935) receptor antagonist. The regional pattern of compensation may be determined by the preferential role of 5-HT(1A) or 5-HT(1B) receptors in regulating 5-HT release. Taken together, these results demonstrate the development of regional plasticity between complementary somatodendritic and terminal autoreceptors after the genetic deletion of 5-HT(1A) or 5-HT(1B) receptors.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
11504806
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"