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: Tomohisa Mori, Toshimasa Itoh, Kazumi Yoshizawa, Yuya Ise, Keisuke Mizuo, Tomoya Saeki, Sachiko Komiya, Daiki Masukawa, Masahiro Shibasaki, Tsutomu Suzuki
• Journal: Addiction biology (Addict Biol) Vol. 20 Issue 4 Pg. 724-32 (Jul 2015) ISSN: 1369-1600 [Electronic] United States
• PMID: 25065832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Society for the Study of Addiction.

Chemical References

• Analgesics, Opioid
• Narcotic Antagonists
• Receptors, Opioid, delta
• Receptors, Opioid, mu
• Naloxone
• Naltrexone
• naltrindole
• Pentazocine

Topics

• Analgesics, Opioid (administration & dosage, chemistry, pharmacology)
• Analysis of Variance
• Animals
• Conditioning, Psychological (drug effects)
• Dose-Response Relationship, Drug
• Isomerism
• Male
• Naloxone (pharmacology)
• Naltrexone (analogs & derivatives, pharmacology)
• Narcotic Antagonists (pharmacology)
• Nucleus Accumbens (drug effects)
• Pain (physiopathology)
• Pentazocine (administration & dosage, chemistry, pharmacology)
• Rats
• Receptors, Opioid, delta (drug effects, physiology)
• Receptors, Opioid, mu (drug effects, physiology)
• Reward