Abstract
Monoamine transporters are the main targets of methamphetamine (METH). Recently, we showed that fluoxetine, a selective serotonin reuptake inhibitor (SSRI), decreased METH conditioned place preference (CPP), suggesting that serotonin transporter (SERT) inhibition reduces the rewarding effects of METH. To further test this hypothesis, in the present study we investigated the effects of additional SSRIs, paroxetine and fluvoxamine, on METH CPP in C57BL/6J mice. In the CPP test, pretreatment with 20 mg/kg paroxetine abolished the CPP for METH, whereas pretreatment with 100 mg/kg fluvoxamine prior to administration of METH failed to inhibit METH CPP. These results suggest that paroxetine, a medication widely used to treat depression, may be a useful tool for treating METH dependence. Further, these data suggest that molecules other than the SERT [such as G protein-activated inwardly rectifying K+ (GIRK) channels] whose activities are modulated by paroxetine and fluoxetine, but not by fluvoxamine, are involved in reducing METH CPP by paroxetine and fluoxetine.
Highlights
Methamphetamine (METH) is abused in worldwide [1]
The two-way analysis of variance (ANOVA) revealed that mice treated with paroxetine during the test phase exhibited decreased conditioned place preference (CPP) scores compared to mice treated with saline during the test phase (F1,72 = 7.888, P < 0.01), whereas mice treated with paroxetine during the conditioning phase did not differ significantly from mice treated with saline during the test phase in the CPP score [F1,72 = 1.704, not significant (n.s.); Fig. (1A)]
We showed that paroxetine, a widely used medication for treating depression, inhibited METH CPP in mice, similar to the results we reported previously with fluoxetine [8]
Summary
Methamphetamine (METH) is abused in worldwide [1]. In Japan, the number of people arrested for METH possession or use is approximately 100 times higher than those arrested for cocaine, opioids, or cannabis. METH frequently induces psychotic states with symptoms similar to those seen in paranoid schizophrenia [2]. Such psychotic states are treated primarily in hospitals resulting in high medical costs. Cocaine administration leads to increases in extracellular dopamine concentration in the striatum of DAT knockout mice but not of DAT/SERT double knockout mice [7]. Taken together, these reports suggest that SERT inhibition may decrease METH and cocaine CPP
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