Inhibitory effects of SA4503 on the rewarding effects of abused drugs

Tomohisa Mori, Mahardian Rahmadi, Kazumi Yoshizawa, Toshimasa Itoh, Masahiro Shibasaki, Tsutomu Suzuki

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Previous findings have shown that sigma-1 receptors (Sig-1Rs) are upregulated by the self-administration of methamphetamine, whereas Sig-1R antisense can attenuate the behavioral effects of psychostimulants in rodents. Sig-1R is an endoplasmic reticulum chaperone protein. However, the effects of Sig-1R agonist on the rewarding effects of abused drugs are not fully understood. Therefore, we examined the effects of selective Sig-1R agonists, such as SA4503 and (+)-pentazocine, on the rewarding effects of abused drugs such as methamphetamine, cocaine and morphine in rats, as measured by the conditioned place preference. Methamphetamine, cocaine and morphine induced a significant place preference. SA4503, but not (+)-pentazocine, significantly attenuated the abused drug-induced place preference. We recently showed that (+)-pentazocine exerts U50,488H-like discriminative stimulus effects, which are related to its psychotomimetic/aversive effects. However, SA4503 did not generalize to the discriminative stimulus effects of U50,488H. These results suggest that SA4503 inhibits the rewarding effects of abused drugs, and that psychotomimetic/aversive effects may not play a role in the attenuating effects of SA4503 on the rewarding effects of abused drugs.

Original languageEnglish
Pages (from-to)362-369
Number of pages8
JournalAddiction Biology
Issue number3
Publication statusPublished - May 2014
Externally publishedYes


  • Abused drugs
  • SA4503
  • sigma-1 receptor


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