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Link to original content: https://pubmed.ncbi.nlm.nih.gov/24561093/
The trace amine associated receptor 1 agonist RO5263397 attenuates the induction of cocaine behavioral sensitization in rats - PubMed Skip to main page content
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. 2014 Apr 30:566:67-71.
doi: 10.1016/j.neulet.2014.02.024. Epub 2014 Feb 21.

The trace amine associated receptor 1 agonist RO5263397 attenuates the induction of cocaine behavioral sensitization in rats

David A Thorn  1 , Chaogui Zhang  2 , Yanan Zhang  3 , Jun-Xu Li  4
Affiliations

The trace amine associated receptor 1 agonist RO5263397 attenuates the induction of cocaine behavioral sensitization in rats

David A Thorn et al. Neurosci Lett. .

Abstract

The trace amine associated receptor (TAAR) 1 is a new G protein coupled receptor that critically modulates central dopaminergic system. Recently, several selective TAAR 1 ligands have been described to possess antipsychotic and antidepressant-like activities. However, it is unknown of the role of these ligands in modulating psychostimulant-induced neurobehavioral plasticity. This study examined the effects of a selective TAAR 1 agonist, RO5263397, on cocaine induced behavioral sensitization in rats, a rodent model of drug-induced behavioral plasticity. Daily treatment with 15mg/kg cocaine (i.p., 7 days) induced robust locomotor sensitization in rats. RO5263397 (1-10mg/kg, i.p.) alone did not significantly alter the locomotor activity. Acute treatment with RO5263397 (3.2 and 10mg/kg) did not significantly modify cocaine-induced hyperactivity; however, the induction of locomotor sensitization was significantly blocked after 7 days of daily RO5263397 treatment. More importantly, the expression of locomotor sensitization remained significantly attenuated when rats were re-tested 7 days after the last drug treatment. The marked attenuation of cocaine sensitization was also evidenced by the suppression of the dose-effect function (3.2-32mg/kg) of cocaine sensitization. Together, these data represent the first to report a critical modulatory role of TAAR 1 agonists in cocaine-induced behavioral plasticity, which may be indicative of its potential role for altering other long-lasting behavioral maladaptations of cocaine including drug addiction.

Keywords: Behavioral sensitization; Cocaine; Rats; TAAR 1.

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Conflict of interest statement

Conflicts of interest

None.

Figures

Figure 1
Figure 1
Effects of RO5263397 on the locomotor activity in rats. Ordinate: locomotion counts/5 min; abscissa: time (min). Inset: total locomotion counts within the period of 60 min. N=12 for control and N=6 for ORG5263397-treated groups.
Figure 2
Figure 2
Effects of RO5263397 on the behavioral sensitization to 15 mg/kg cocaine in rats. Ordinate: total locomotion counts/60 min. Coc: Cocaine; RO: RO5263397; Veh: Vehicle. ** P < 0.01 as compared to 15 Coc/Veh group; *** P < 0.001 as compared to 15 Coc./Veh group. N= 7–8/group.
Figure 3
Figure 3
Effects of RO5263397 on the behavioral sensitization to cocaine in rats. Ordinate: total locomotion counts/15 min; abscissa: cumulative doses of cocaine (mg/kg). *** P < 0.0001 as compared to corresponding cocaine dose without RO5263397 pretreatment. N= 8/group.
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