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
European journal of pharmacology November 15, 2013 DOI: 10.1016/j.ejphar.2013.10.050 via PubMed
Summary
AI-generated from the abstractActivating the κ opioid receptor with the salvinorin A analogue 2-methoxy-methyl salvinorin B (MOM Sal B) at 0.3 mg/kg reduced cocaine-seeking behavior in rats, but also reduced sucrose reinforcement. No sedation was observed—locomotion in cocaine-induced hyperactivity and open field tests was unchanged—yet the forced swim test showed increased immobility and decreased swimming times, indicating pro-depressive effects. The compound thus modulates cocaine-seeking non-selectively without sedation, but depressive side effects may limit its therapeutic use.
Study at a glance
| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | 2-methoxy-methyl salvinorin B (MOM Sal B) |
| Dose | 0.3 mg/kg |
| Topics | Salvia divinorum |
| Keywords | Cocaine Forced swim test Locomotion Self-administration |
| Key finding | MOM Sal B attenuates cocaine-seeking behavior non-selectively without sedation but produces pro-depressive effects. |
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 (0.3mg/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.