Selective activation of the trace amine-associated receptor 1 decreases cocaine's reinforcing efficacy and prevents cocaine-induced changes in brain reward thresholds

Pei, Yue; Mortas, P.; Hoener, Marius C.; Canales, Juan J.

doi:10.1016/j.pnpbp.2015.05.014

Cited by 51 publications

(31 citation statements)

References 47 publications

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“…The TAAR1 system has been reported to regulate the behavioral actions of drugs of abuse. Indeed, consistent with our results, TAAR1 agonists were shown to be able to block cocaine seeking (Pei et al, 2014), suppress the reinforcing and rewarding effects of cocaine (Pei et al, 2015), attenuate cocaine behavioral sensitization, and reinstatement of cocaine seeking, as well as the expression of cocaineinduced CPP (Liu et al, 2016;Thorn et al, 2014). In line with the results from the pharmacological studies, TAAR1 KO mice display heightened locomotor response and context-dependent locomotor sensitization to amphetamine, and increased sensitivity to reinstatement of amphetamineinduced CPP, and they consume more alcohol and methamphetamine, compared with wild-type mice (Harkness et al, 2015;Lindemann et al, 2008;Lynch et al, 2013;Sukhanov et al, 2016;Wolinsky et al, 2007).…”

Section: Discussionsupporting

confidence: 91%

“…Growing evidence suggests that TAAR1 has a major role in regulating the behavioral actions of drugs of abuse, in particular those of psychostimulants. Indeed, both gene deletion and pharmacological studies have shown that TAAR1 activation reduces the reinforcing and rewarding effects of cocaine and methamphetamine, their locomotor stimulant effects, as well as reinstatement of seeking behavior (Harkness et al, 2015;Liu et al, 2016;Pei et al, 2015;Sukhanov et al, 2016;Thorn et al, 2014;Wolinsky et al, 2007). These actions are thought to occur via a TAAR1mediated negative modulation of dopaminergic transmission in the mesocorticolimbic system (Espinoza et al, 2015;Miller et al, 2005;Xie et al, 2007); particularly, lack of TAAR1 has been shown to result in an elevated dopaminergic firing rate, whereas TAAR1 activation suppresses such firing (Bradaia et al, 2009;Lindemann et al, 2008;Revel et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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The Trace Amine-Associated Receptor 1 Agonist RO5256390 Blocks Compulsive, Binge-like Eating in Rats

Ferragud

Howell

Moore

et al. 2016

Neuropsychopharmacol

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Compulsive, binge eating of highly palatable food constitutes a core feature of some forms of obesity and eating disorders, as well as of the recently proposed disorder of food addiction. Trace amine-associated receptor 1 (TAAR1) is a highly conserved G-protein-coupled receptor bound by endogenous trace amines. TAAR1 agonists have been shown to reduce multiple behavioral effects of drugs of abuse through their actions on the mesocorticolimbic system. In this study, we hypothesized that TAAR1 may have a role in compulsive, binge-like eating; we tested this hypothesis by assessing the effects of a TAAR1 agonist, RO5256390, in multiple excessive feeding-related behaviors induced by limiting access to a highly palatable diet in rats. Our results show that RO5256390 blocked binge-like eating in rats responding 1 h per day for a highly palatable sugary diet. Consistent with a palatability-selective effect, drug treatment selectively reduced the rate and regularity of palatable food responding, but it did not affect either baseline intake or food restriction-induced overeating of the standard chow diet. Furthermore, RO5256390 fully blocked compulsive-like eating when the palatable diet was offered in an aversive compartment of a light/dark conflict box, and blocked the conditioned rewarding properties of palatable food, as well as palatable food-seeking behavior in a second-order schedule of reinforcement. Drug treatment had no effect on either anxiety-like or depressive-like behavior, and it did not affect control performance in any of the tests. Importantly, rats exposed to palatable food showed decreased TAAR1 levels in the medial prefrontal cortex (mPFC), and RO5256390 microinfused into the infralimbic, but not prelimbic, subregion of the mPFC-reduced binge-like eating. Altogether, these results provide evidence for TAAR1 agonism as a novel pharmacological treatment for compulsive, binge eating.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

The Trace Amine-Associated Receptor 1 Agonist RO5256390 Blocks Compulsive, Binge-like Eating in Rats

Ferragud

Howell

Moore

et al. 2016

Neuropsychopharmacol

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“…Many psychoactive compounds bind to TAAR 1 (Bunzow et al, 2001;Simmler et al, 2013;Simmler et al, 2016), a potential target for the treatment of addiction (Cotter et al, 2015;Jing and Li, 2015;Pei et al, 2015). Psilocin, DMT, 4-OH-MET, and 5-MeO-AMT had low-micromolar affinity to TAAR 1rat .…”

Section: Discussionmentioning

confidence: 99%

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

Rickli

Moning

Hoener

et al. 2016

European Neuropsychopharmacology

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271

266

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“…Selective TAAR1 full and partial agonists have procognitive, stress-reducing, and antipsychotic-like properties in rodents and non-human primates (Revel et al, 2012b(Revel et al, , 2013. More recent studies have implicated TAAR1 in addiction (Pei et al, 2014(Pei et al, , 2015 and metabolic regulation (Raab et al, 2016). TAAR1 partial agonists also dose-dependently increase wakefulness in rats, suggesting a role for TAAR1 in regulating wakefulness (Revel et al, 2012b(Revel et al, , 2013.…”

Section: Introductionmentioning

confidence: 99%

Trace Amine-Associated Receptor 1 Regulates Wakefulness and EEG Spectral Composition

Schwartz

Black

Fisher

et al. 2016

Neuropsychopharmacol

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Trace amine-associated receptor 1 (TAAR1) agonists have been shown to have procognitive, antipsychotic-like, anxiolytic, weight-reducing, glucose-lowering, and wake-promoting activities. We used Taar1 knockout (KO) and overexpressing (OE) mice and TAAR1 agonists to elucidate the role of TAAR1 in sleep/wake. EEG, EMG, body temperature (T), and locomotor activity (LMA) were recorded in Taar1 KO, OE, and WT mice. Following a 24 h recording to characterize basal sleep/wake parameters, mice were sleep deprived (SD) for 6 h. In another experiment, mice were given three doses of the TAAR1 partial agonist RO5263397, caffeine, or vehicle p.o. Baseline wakefulness was modestly increased in OE compared with WT mice. Baseline theta (4.5-9 Hz) and low gamma (30-60 Hz) activity was elevated in KO compared with OE mice in NREM and REM sleep. Following SD, both KO and OE mice exhibited a homeostatic sleep rebound. In WT mice, RO5263397 increased waking and reduced NREM and REM sleep, decreased gamma power during wake and NREM, and decreased T without affecting LMA; these effects were absent in KO mice and potentiated in OE mice. In contrast, caffeine increased wake time, NREM gamma power, and LMA in all strains compared with vehicle; this effect was attenuated in KO and potentiated in OE mice. TAAR1 overexpression modestly increases wakefulness, whereas TAAR1 partial agonism increases wakefulness and also reduces NREM and also REM sleep. These results indicate a modulatory role for TAAR1 in sleep/wake and cortical activity and suggest TAAR1 as a novel target for wake-promoting therapeutics.

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Selective activation of the trace amine-associated receptor 1 decreases cocaine's reinforcing efficacy and prevents cocaine-induced changes in brain reward thresholds

Cited by 51 publications

References 47 publications

The Trace Amine-Associated Receptor 1 Agonist RO5256390 Blocks Compulsive, Binge-like Eating in Rats

The Trace Amine-Associated Receptor 1 Agonist RO5256390 Blocks Compulsive, Binge-like Eating in Rats

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

Trace Amine-Associated Receptor 1 Regulates Wakefulness and EEG Spectral Composition

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