Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylenedioxymethamphetamine ("Ecstasy") in serotonin transporter-deficient mice.

Molecular pharmacology | Apr 6, 1998

http://www.ncbi.nlm.nih.gov/pubmed/9547354

The sodium-dependent, high affinity serotonin [5-hydroxytryptamine (5-HT)] transporter (5-HTT) provides the primary mechanism for inactivation of 5-HT after its release into the synaptic cleft. To further evaluate the function of the 5-HTT, the murine gene was disrupted by homologous recombination. Despite evidence that excess extracellular 5-HT during embryonic development, including that produced by drugs that inhibit the 5-HTT, may lead to severe craniofacial and cardiac malformations, no obvious developmental phenotype was observed in the 5-HTT-/- mice. High affinity [3H]5-HT uptake was completely absent in 5-HTT-/- mice, confirming a physiologically effective knockout of the 5-HTT gene. 5-HTT binding sites labeled with [125I] 3 beta-(4'-iodophenyl)tropan-2 beta-carboxylic acid methyl ester were reduced in a gene dose-dependent manner, with no demonstrable binding in 5-HTT-/- mutants. In adult 5-HTT-/- mice, marked reductions (60-80%) in 5-HT concentrations were measured in several brain regions. While (+)-amphetamine-induced hyperactivity did not differ across genotypes, the locomotor enhancing effects of (+)-3, 4-methylenedioxymethamphetamine, a substituted amphetamine that releases 5-HT via a transporter-dependent mechanism, was completely absent in 5-HTT-/- mutants. Together, these data suggest that the presence of a functional 5-HTT is essential for brain 5-HT homeostasis and for 3,4-methylenedioxymethamphetamine-induced hyperactivity.

Pubmed ID: 9547354 RIS Download

Mesh terms: Animals | Autoradiography | Brain Chemistry | Carrier Proteins | Female | Gene Targeting | Genotype | Homeostasis | Locomotion | Male | Membrane Glycoproteins | Membrane Transport Proteins | Mice | Mice, Inbred C57BL | Mice, Inbred Strains | Mice, Knockout | Microinjections | N-Methyl-3,4-methylenedioxyamphetamine | Nerve Tissue Proteins | Serotonin | Serotonin Plasma Membrane Transport Proteins

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.