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The 2-Methoxy methyl analogue of salvinorin A attenuates cocaine-induced drug seeking and sucrose reinforcements in rats
Morani, Aashish S. Ewald, Amy Prevatt-Smith, Katherine M. Prisinzano, Thomas E. Kivell, Bronwyn
Morani, Aashish S.
Ewald, Amy
Prevatt-Smith, Katherine M.
Prisinzano, Thomas E.
Kivell, Bronwyn
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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-methoxymethyl 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.
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Date
2013-11-04
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Elsevier
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Keywords
Cocaine, Self-administration, Salvinorin A, Sucrose reinforcement, Locomotion, Forced swim test
Citation
Morani, Aashish S., Amy Ewald, Katherine M. Prevatt-Smith, Thomas E. Prisinzano, and Bronwyn M. Kivell. "The 2-methoxy Methyl Analogue of Salvinorin A Attenuates Cocaine-induced Drug Seeking and Sucrose Reinforcements in Rats." European Journal of Pharmacology 720.1-3 (2013): 69-76.