Effects of β-Phenylethylamine on Psychomotor, Rewarding, and Reinforcing Behaviors and Affective State: The Role of Dopamine D1 Receptors.

In Soo Ryu,Tae Wan Kim,Ri-Na Lim,Joung-Wook Seo,Eun Sang Choe,Sumin Sohn,Oc-Hee Kim,Ji Sun Kim,Eun Young Jang

doi:10.3390/ijms22179485

In Soo Ryu, Tae Wan Kim + Show 7 more

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https://doi.org/10.3390/ijms22179485

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Abstract

Beta-phenylethylamine (β-PEA) is a well-known and widespread endogenous neuroactive trace amine found throughout the central nervous system in humans. In this study, we demonstrated the effects of β-PEA on psychomotor, rewarding, and reinforcing behaviors and affective state using the open-field test, conditioned place preference (CPP), self-administration, and ultrasonic vocalizations (USVs) paradigms. We also investigated the role of the dopamine (DA) D1 receptor in the behavioral effects of β-PEA in rodents. Using enzyme-linked immunosorbent assay (ELISA) and Western immunoblotting, we also determined the DA concentration and the DA-related protein levels in the dorsal striatum of mice administered with acute β-PEA. The results showed that acute β-PEA increased stereotypic behaviors such as circling and head-twitching responses in mice. In the CPP experiment, β-PEA increased place preference in mice. In the self-administration test, β-PEA significantly enhanced self-administration during a 2 h session under fixed ratio (FR) schedules (FR1 and FR3) and produced a higher breakpoint during a 6 h session under progressive ratio schedules of reinforcement in rats. In addition, acute β-PEA increased 50-kHz USV calls in rats. Furthermore, acute β-PEA administration increased DA concentration and p-DAT and TH expression in the dorsal striatum of mice. Finally, pretreatment with SCH23390, a DA D1 receptor antagonist, attenuated β-PEA-induced circling behavior and β-PEA-taking behavior in rodents. Taken together, these findings suggest that β-PEA has rewarding and reinforcing effects and psychoactive properties, which induce psychomotor behaviors and a positive affective state by activating the DA D1 receptor in the dorsal striatum.

Highlights

Beta-phenylethylamine (β-PEA) is well known as an endogenous neuroactive trace amine and is widespread throughout the central nervous system of rodents [1]
The results showed that 50 mg/kg β-PEA, but not 3, 10, and 30 mg/kg, significantly increased the circling behavior compared to the saline control group (Figure 1B,C; F(4,40) = 10.74, p < 0.001, 50 mg/kg β-PEA: p < 0.001)
Since the stimulation of DA D1 receptor (DAD1R) is closely associated with the enhancement of dopaminergic neurotransmission in the brain, leading to the reinforcing effects of drugs [31,32], we investigated whether the pharmacological prevention of DAD1R alters the reinforcing effects of β-PEA using a self-administration paradigm

Summary

Introduction

Beta-phenylethylamine (β-PEA) is well known as an endogenous neuroactive trace amine and is widespread throughout the central nervous system of rodents [1]. Β-PEA is synthesized within nigrostriatal and mesolimbic dopamine (DA) regions, such as the striatum and nucleus accumbens [2], and the highest level of β-PEA is found in these brain regions [3,4]. It is known that β-PEA inhibits the uptake of DA and promotes the release of DA in the mesocorticolimbic pathway [5,6]. In previous studies, systemic injection or intrastriatal infusion of β-PEA increased DA levels in the striatum [8] and nucleus accumbens [9], and β-PEA and amphetamine induced similar levels of DA release in neuronal culture [10]

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