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

doi:10.1016/j.ejphar.2013.10.050

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 journal › Article › peer-review

16 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 language	English
Pages (from-to)	69-76
Number of pages	8
Journal	European Journal of Pharmacology
Volume	720
Issue number	1-3
DOIs	https://doi.org/10.1016/j.ejphar.2013.10.050
State	Published - 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

Access to Document

10.1016/j.ejphar.2013.10.050

Cite this

@article{d8c237f4975d47a685339f71f0d798a8,

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

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.",

keywords = "Cocaine, Forced swim test, Locomotion, Salvinorin A, Self-administration, Sucrose reinforcement",

author = "Morani, {Aashish S.} and Amy Ewald and Prevatt-Smith, {Katherine M.} and Prisinzano, {Thomas E.} and Kivell, {Bronwyn M.}",

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.",

year = "2013",

month = nov,

day = "15",

doi = "10.1016/j.ejphar.2013.10.050",

language = "English",

volume = "720",

pages = "69--76",

number = "1-3",

}

TY - JOUR

T1 - The 2-methoxy methyl analogue of salvinorin A attenuates cocaine-induced drug seeking and sucrose reinforcements in rats

AU - Morani, Aashish S.

AU - Ewald, Amy

AU - Prevatt-Smith, Katherine M.

AU - Prisinzano, Thomas E.

AU - Kivell, Bronwyn M.

N1 - 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.

PY - 2013/11/15

Y1 - 2013/11/15

N2 - 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.

AB - 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.

KW - Cocaine

KW - Forced swim test

KW - Locomotion

KW - Salvinorin A

KW - Self-administration

KW - Sucrose reinforcement

UR - http://www.scopus.com/inward/record.url?scp=84890117454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890117454&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2013.10.050

DO - 10.1016/j.ejphar.2013.10.050

M3 - Article

C2 - 24201308

AN - SCOPUS:84890117454

SN - 0014-2999

VL - 720

SP - 69

EP - 76

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

IS - 1-3

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this