The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity

Miller, Gregory M.

doi:10.1111/j.1471-4159.2010.07109.x

Cited by 216 publications

(196 citation statements)

References 82 publications

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“…These genes are not located on mouse chromosome 10, and are therefore not candidates for the QTG in that region (Belknap et al, 2013). However, Taar1 is within the QTL interval, and it modulates monoamine levels by altering transporter function in mice and primates (Miller, 2011(Miller, ,2012Revel et al, 2011;Miller, 2008,2009). Furthermore, Taar1 − / − mice exhibit lower basal levels and greater amphetamine-induced release of DA in the striatum, compared with +/+ mice (Lindemann et al, 2008;Wolinsky et al, 2007).…”

Section: Taar1 and Methamphetamine Intakementioning

confidence: 99%

Trace Amine-Associated Receptor 1 Regulation of Methamphetamine Intake and Related Traits

Harkness

Shi

Janowsky

et al. 2015

Neuropsychopharmacol

149

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Continued methamphetamine (MA) use is dependent on a positive MA experience and is likely attenuated by sensitivity to the aversive effects of MA. Bidirectional selective breeding of mice for high (MAHDR) or low (MALDR) voluntary consumption of MA demonstrates a genetic influence on MA intake. Quantitative trait locus (QTL) mapping identified a QTL on mouse chromosome 10 that accounts for greater than 50% of the genetically-determined differences in MA intake in the MAHDR and MALDR lines. The trace amine-associated receptor 1 gene (Taar1) is within the confidence interval of the QTL and encodes a receptor (TAAR1) that modulates monoamine neurotransmission and at which MA serves as an agonist. We demonstrate the existence of a non-functional allele of Taar1 in the DBA/2J mouse strain, one of the founder strains of the selected lines, and show that this non-functional allele co-segregates with high MA drinking and with reduced sensitivity to MA-induced conditioned taste aversion (CTA) and hypothermia. The functional Taar1 allele, derived from the other founder strain, C57BL/6J, segregates with low MA drinking and heightened sensitivity to MA-induced CTA and hypothermia. A role for TAAR1 in these phenotypes is corroborated in Taar1 transgenic mice: Taar1 knockout mice consume more MA and exhibit insensitivity to MA-induced CTA and hypothermia, compared with Taar1 wild-type mice. These are the first data to show that voluntary MA consumption is, in part, regulated by TAAR1 function. Behavioral and physiological studies indicate that TAAR1 function increases sensitivity to aversive effects of MA, and may thereby protect against MA use.

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Section: Taar1 and Methamphetamine Intakementioning

confidence: 99%

Trace Amine-Associated Receptor 1 Regulation of Methamphetamine Intake and Related Traits

Harkness

Shi

Janowsky

et al. 2015

Neuropsychopharmacol

149

View full text Add to dashboard Cite

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“…Cloning of trace amine receptors in 2001 [23,24], elicited enormous efforts for exploring signal transduction of these G-protein coupled receptors whose genes are located on chromosome focus 6q23.1 [25]. The receptors have been shown to co-localize with dopamine or adrenaline transporters in monoamine neurons and to modulate the functions of monoamines [26][27][28].…”

Section: Trace Amine-associated Receptor Type 1 (Taar1)mentioning

confidence: 99%

Are D-Neurons and Trace Amine-Associated Receptor, Type 1 Involved in Mesolimbic Dopamine Hyperactivity of Schizophrenia?

Ikemoto¹

2012

Med Chem

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Although dopamine (DA) dysfunction is a well-known hypothesis for etiology of schizophrenia, molecular basis of mesolimbic DA hyperactivity has not yet been clarified. To explain this, modulating function of trace amines on DA neurotransmission and the decreased number of striatal D-neurons, trace amine-producing neurons, were considered. Notably, Trace Amine-Associated Receptor, Type 1 (TAAR1), a subtype of trace amine receptors, has a large number of ligands, including tyramine, β-phenylethylamine and methamphetamine that influence on human mental state, and is now regarded as a target receptor for novel neuroleptics. Reduced stimulation of TAAR1 on DA neurons in the midbrain ventral tegmental area (VTA) has been revealed to increase firing frequency of VTA DA neurons. The author and her colleagues reported the decrease of D-neurons in the striatum and nucleus accumbens of postmortem brains of patients with schizophrenia. This may imply the decrease of trace amine synthesis and consequent reduction of the stimulation of TAAR1 on terminals of midbrain VTA DA neurons, and may lead to mesolimbic DA hyperactivity in schizophrenia. The decrease of striatal D-neurons of postmortem brains of schizophrenia might be due to neural stem cell dysfunction in the subventricular zone of lateral ventricle. The new "D-cell hypothesis", in which D-neurons and TAAR1 are involved, may explain mesolimbic DA hyperactivity of schizophrenia.

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Section: Trace Amine-associated Receptor Type 1 (Taar1)mentioning

confidence: 99%

“…The trace amine-associated receptor, type 1 (TAAR1) has a large number of ligands, including tyramine, β-phenylethylamine (PEA)and psychostimulants, for example, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and lysergic acid diethylamide (LSD) [23,25,29] (Table 1), and is now a target receptor for exploring novel neuroleptics [30,31].…”

Section: Trace Amine-associated Receptor Type 1 (Taar1)mentioning

confidence: 99%

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Why D-neuron? Importance in schizophrenia research

Ikemoto¹

2012

OJPsych

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The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity

Cited by 216 publications

References 82 publications

Trace Amine-Associated Receptor 1 Regulation of Methamphetamine Intake and Related Traits

Trace Amine-Associated Receptor 1 Regulation of Methamphetamine Intake and Related Traits

Are D-Neurons and Trace Amine-Associated Receptor, Type 1 Involved in Mesolimbic Dopamine Hyperactivity of Schizophrenia?

Why D-neuron? Importance in schizophrenia research

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