title: Involvement of μ- and δ-opioid receptor function in the rewarding effect of (±)-pentazocine.
abstract: Most opioid receptor agonists have abuse potential, and the rewarding effects of opioids can be reduced in the presence of pain. While each of the enantiomers of pentazocine has a differential pharmacologic profile, (±)-pentazocine has been used clinically for the treatment of pain. However, little information is available regarding which components of pentazocine are associated with its rewarding effects, and whether the (±)-pentazocine-induced rewarding effects can be suppressed under pain. Therefore, the present study was performed to investigate the effects of pain on the acquisition of the rewarding effects of (±)-pentazocine, and to examine the mechanism of the rewarding effects of (±)-pentazocine using the conditioned place preference paradigm. (±)-Pentazocine and (-)-pentazocine, but not (+)-pentazocine, produced significant rewarding effects. Even though the rewarding effects induced by (±)-pentazocine were significantly suppressed under pain induced by formalin, accompanied by increase of preprodynorphin mRNA levels in the nucleus accumbens, a high dose of (±)-pentazocine produced significant rewarding effects under pain. In the normal condition, (±)-pentazocine-induced rewarding effects were blocked by a low dose of naloxone, whereas the rewarding effects induced by high doses of pentazocine under pain were suppressed by naltrindole (a δ-opioid receptor antagonist). Interestingly, (±)-pentazocine did not significantly affect dopamine levels in the nucleus accumbens. These findings suggest that the rewarding effects of (-)-pentazocine may contribute to the abuse potential of (±)-pentazocine through μ- as well as δ-opioid receptors, without robust activation of the mesolimbic dopaminergic system. We also found that neural adaptations can reduce the abuse potential of (±)-pentazocine under pain.
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Tomohisa
authors: T
authors: Mori
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Toshimasa
authors: T
authors: Itoh
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Kazumi
authors: K
authors: Yoshizawa
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Yuya
authors: Y
authors: Ise
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Keisuke
authors: K
authors: Mizuo
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Tomoya
authors: T
authors: Saeki
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Sachiko
authors: S
authors: Komiya
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Daiki
authors: D
authors: Masukawa
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Masahiro
authors: M
authors: Shibasaki
authors: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
authors: Tsutomu
authors: T
authors: Suzuki
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007536:Isomerism; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects; D010146:Pain / Q000503:physiopathology*; D010423:Pentazocine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology*; D012201:Reward
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009271:Naltrexone; C055382:naltrindole; D010423:Pentazocine
keywords: Opioid receptor; pentazocine; rewarding effect