Abstract
The recent identification of the trace amine-associated receptor (TAAR)1 provides an opportunity to dissociate the effects of trace amines on the dopamine transporter from receptor-mediated effects. To separate both effects on a physiological level, a Taar1 knockout mouse line was generated. Taar1 knockout mice display increased sensitivity to amphetamine as revealed by enhanced amphetamine-triggered increases in locomotor activity and augmented striatal release of dopamine compared with wild-type animals. Under baseline conditions, locomotion and extracellular striatal dopamine levels were similar between Taar1 knockout and wild-type mice. Electrophysiological recordings revealed an elevated spontaneous firing rate of dopaminergic neurons in the ventral tegmental area of Taar1 knock-out mice. The endogenous TAAR1 agonist p-tyramine specifically decreased the spike frequency of these neurons in wild-type but not in Taar1 knockout mice, consistent with the prominent expression of Taar1 in the ventral tegmental area. Taken together, the data reveal TAAR1 as regulator of dopaminergic neurotransmission.
Footnotes
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This work was supported by F. Hoffmann-La Roche Ltd. and the Swiss Science Foundation Grant 3100-067100.01 (to B.B.).
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.132647.
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ABBREVIATIONS: TAAR, trace amine-associated receptor; kb, kilobase(s); PCR, polymerase chain reaction; NLS, nuclear localization signal; ES, embryonic stem; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; RT, reverse transcription; PBS, phosphate-buffered saline; DOPAC, 3,4-dihydroxyphenylacetic acid; 5-HIAA, 5-hydroxyindoleacetic acid; HPLC, high-performance liquid chromatography; GBR 12935, 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine.
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↵ The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.
- Received October 9, 2007.
- Accepted December 13, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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