The 2-methoxy methyl analogue of salvinorin A attenuates cocaine-induced drug seeking and sucrose reinforcements in rats

Aashish S. Morani, Amy Ewald, Katherine M. Prevatt-Smith, Thomas E. Prisinzano, Bronwyn M. Kivell

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

κ Opioid receptor activation by traditional arylacetamide agonists and the novel neoclerodane diterpene κ opioid receptor agonist Salvinorin A (Sal A) results in attenuation of cocaine-seeking behavior in pre-clinical models of addiction. However, adverse effects such as sedation, depression and aversion limit their clinical utility. The Sal A analogue, 2-methoxy-methyl salvinorin B (MOM Sal B) is a longer acting Sal A analogue with high affinity for κ opioid receptors. In this study, we tested MOM Sal B for its ability to modulate cocaine-seeking behavior in rats. MOM Sal B (0.3 mg/kg) successfully attenuated cocaine-seeking but also attenuated sucrose reinforcement. No change in activity was observed in either cocaine-induced hyperactivity or spontaneous open field activity tests but increased immobility and decreased swimming times in the forced swim test were observed. This study indicates that κ opioid receptor activation by more potent Sal A analogues modulates cocaine-seeking behavior non-selectively without causing sedation, suggesting an improved side effects profile. However, pro-depressive effects are seen, which may limit the therapeutic potential of this compound. Future studies with Sal A analogues having affinities at other opioid receptors are warranted as they have the potential to identify compounds having effective anti-addiction properties.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalEuropean Journal of Pharmacology
Volume720
Issue number1-3
DOIs
StatePublished - Nov 15 2013

Bibliographical note

Funding Information:
The authors would like to thank the Health Research Council of NZ , Neurological Foundation of NZ , and National Institute on Drug Abuse ( DA018151 to TEP) for funding this study. The content is the sole responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse, National Institutes of Health. The authors would like to acknowledge the assistance of Prof. Susan Schenk, Mr. Richard Moore, Mr. Caleb Carati and Mr. Alex Crowther.

Keywords

  • Cocaine
  • Forced swim test
  • Locomotion
  • Salvinorin A
  • Self-administration
  • Sucrose reinforcement

ASJC Scopus subject areas

  • Pharmacology

Fingerprint

Dive into the research topics of 'The 2-methoxy methyl analogue of salvinorin A attenuates cocaine-induced drug seeking and sucrose reinforcements in rats'. Together they form a unique fingerprint.

Cite this