title: Inhibitory effects of SA4503 on the rewarding effects of abused drugs.
abstract: 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.
authors.affiliation: Department of Toxicology, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Mori
authors.forename: Mahardian
authors.initials: M
authors.lastname: Rahmadi
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Itoh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shibasaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007266:Inhibition, Psychological; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D010423:Pentazocine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012201:Reward; D019966:Substance-Related Disorders / Q000188:drug therapy
chemical_list: D018765:Dopamine Uptake Inhibitors; D009294:Narcotics; D018697:Nootropic Agents; D010879:Piperazines; D008694:Methamphetamine; D009020:Morphine; C101789:SA 4503; D003042:Cocaine; D010423:Pentazocine