Trace amine-associated receptor 1 modulates dopaminergic activity.
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.
Lindemann
Lothar
L
Pharmaceuticals Division, Central Nervous System Research, Department PRDNP5 CH, Bldg. 70/331, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland.
Meyer
Claas Aiko
CA
Jeanneau
Karine
K
Bradaia
Amyaouch
A
Ozmen
Laurence
L
Bluethmann
Horst
H
Bettler
Bernhard
B
Wettstein
Joseph G
JG
Borroni
Edilio
E
Moreau
Jean-Luc
JL
Hoener
Marius C
MC
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018492:Dopamine Antagonists / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000095383:Trace Amine-Associated Receptors
D000661:Amphetamine; D004298:Dopamine; D018492:Dopamine Antagonists; D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors