The calpain inhibitor A-705253 attenuates alcohol-seeking and relapse with low side-effect profile
Preclinical studies revealed contribution of N-methyl-D-aspartate receptors (NMDARs) to a variety of neuropsychiatric diseases including alcoholism, but development of NMDAR antagonists for therapeutic use has been a challenge, in part due to severe side effects. One of the key intracellular events...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
2016
|
| In: |
Neuropsychopharmacology
Year: 2015, Volume: 41, Issue: 4, Pages: 979-988 |
| ISSN: | 1740-634X |
| DOI: | 10.1038/npp.2015.225 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1038/npp.2015.225 Verlag, Volltext: https://www-nature-com.ezproxy.medma.uni-heidelberg.de/articles/npp2015225 
|
| Author Notes: | Valentina Vengeliene, Achim Moeller, Marcus W. Meinhardt, Patrick M. Beardsley, Wolfgang H. Sommer, Rainer Spanagel and Anton Bespalov |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1662464932 | ||
| 003 | DE-627 | ||
| 005 | 20230426172412.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 190327r20162015xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/npp.2015.225 |2 doi | |
| 035 | |a (DE-627)1662464932 | ||
| 035 | |a (DE-599)KXP1662464932 | ||
| 035 | |a (OCoLC)1341205559 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Vengeliene, Valentina |e VerfasserIn |0 (DE-588)130680516 |0 (DE-627)505582236 |0 (DE-576)298340542 |4 aut | |
| 245 | 1 | 4 | |a The calpain inhibitor A-705253 attenuates alcohol-seeking and relapse with low side-effect profile |c Valentina Vengeliene, Achim Moeller, Marcus W. Meinhardt, Patrick M. Beardsley, Wolfgang H. Sommer, Rainer Spanagel and Anton Bespalov |
| 264 | 1 | |c 2016 | |
| 300 | |a 10 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 27.03.2019 | ||
| 500 | |a Published online 16 September 2015 | ||
| 520 | |a Preclinical studies revealed contribution of N-methyl-D-aspartate receptors (NMDARs) to a variety of neuropsychiatric diseases including alcoholism, but development of NMDAR antagonists for therapeutic use has been a challenge, in part due to severe side effects. One of the key intracellular events resulting from stimulation of NMDAR is activation of calpains-calcium-dependent cysteine proteases. Here we studied whether inhibition of calpains would produce therapeutic-like effects of NMDAR antagonists but without their NMDAR-mediated side-effect profile. The calpain inhibitor A-705253 (3-10 mg/kg) was tested in a model of cue-induced reinstatement of alcohol-seeking behavior in post-dependent Wistar rats and in an alcohol deprivation effect (ADE) model in long-term alcohol drinking Wistar rats, two behavioral models for alcohol-seeking and relapse, respectively. We also tested the effect of A-705253 on the saccharine deprivation effect (SDE) as a selectivity measure. Acute treatment with A-705253 dose-dependently reduced cue-induced reinstatement of alcohol-seeking behavior. Repeated administration of A-705253 caused significant reductions of relapse-like excessive alcohol intake during the post-abstinence drinking days, an effect that persisted during two more successive drug-free drinking weeks, which was selective for the ADE as the SDE was unaffected. However, A-705253 did not produce psychostimulant, cognition impairing (delayed-matching-to-position), or psychotomimetic effects (specifically, phencyclidine discriminative stimulus effects). Taken together, these results demonstrate the involvement of calpains in alcohol-seeking and relapse and present a rationale for a novel pharmacological intervention that may reduce craving and relapse with minimal side effects in alcohol-dependent patients. | ||
| 534 | |c 2015 | ||
| 700 | 1 | |a Sommer, Wolfgang H. |e VerfasserIn |0 (DE-588)1025859626 |0 (DE-627)725315350 |0 (DE-576)370844076 |4 aut | |
| 700 | 1 | |a Spanagel, Rainer |d 1961- |e VerfasserIn |0 (DE-588)112706312 |0 (DE-627)521941261 |0 (DE-576)289740002 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neuropsychopharmacology |d London : Springer Nature, 1993 |g 41(2016), 4, Seite 979-988 |h Online-Ressource |w (DE-627)320469190 |w (DE-600)2008300-2 |w (DE-576)096188707 |x 1740-634X |7 nnas |a The calpain inhibitor A-705253 attenuates alcohol-seeking and relapse with low side-effect profile |
| 773 | 1 | 8 | |g volume:41 |g year:2016 |g number:4 |g pages:979-988 |g extent:10 |a The calpain inhibitor A-705253 attenuates alcohol-seeking and relapse with low side-effect profile |
| 856 | 4 | 0 | |u https://doi.org/10.1038/npp.2015.225 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u https://www-nature-com.ezproxy.medma.uni-heidelberg.de/articles/npp2015225 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20190327 | ||
| 993 | |a Article | ||
| 994 | |a 2016 | ||
| 998 | |g 112706312 |a Spanagel, Rainer |m 112706312:Spanagel, Rainer |d 60000 |e 60000PS112706312 |k 0/60000/ |p 6 | ||
| 998 | |g 1025859626 |a Sommer, Wolfgang H. |m 1025859626:Sommer, Wolfgang H. |d 60000 |e 60000PS1025859626 |k 0/60000/ |p 5 | ||
| 999 | |a KXP-PPN1662464932 |e 3417185203 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"physDesc":[{"extent":"10 S."}],"origin":[{"dateIssuedDisp":"2016","dateIssuedKey":"2016"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"title":[{"title_sort":"calpain inhibitor A-705253 attenuates alcohol-seeking and relapse with low side-effect profile","title":"The calpain inhibitor A-705253 attenuates alcohol-seeking and relapse with low side-effect profile"}],"language":["eng"],"name":{"displayForm":["Valentina Vengeliene, Achim Moeller, Marcus W. Meinhardt, Patrick M. Beardsley, Wolfgang H. Sommer, Rainer Spanagel and Anton Bespalov"]},"note":["Gesehen am 27.03.2019","Published online 16 September 2015"],"id":{"doi":["10.1038/npp.2015.225"],"eki":["1662464932"]},"person":[{"given":"Valentina","display":"Vengeliene, Valentina","family":"Vengeliene","roleDisplay":"VerfasserIn","role":"aut"},{"family":"Sommer","display":"Sommer, Wolfgang H.","role":"aut","roleDisplay":"VerfasserIn","given":"Wolfgang H."},{"given":"Rainer","roleDisplay":"VerfasserIn","role":"aut","family":"Spanagel","display":"Spanagel, Rainer"}],"relHost":[{"part":{"text":"41(2016), 4, Seite 979-988","issue":"4","year":"2016","pages":"979-988","volume":"41","extent":"10"},"type":{"bibl":"periodical","media":"Online-Ressource"},"pubHistory":["Nachgewiesen 8.1993 -"],"origin":[{"publisherPlace":"London ; Amsterdam [u.a.] ; London","dateIssuedDisp":"1993-","dateIssuedKey":"1993","publisher":"Springer Nature ; Elsevier Science ; Nature Publ. Group"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"issn":["1740-634X"],"zdb":["2008300-2"],"eki":["320469190"]},"recId":"320469190","note":["Ungezählte Beil.: Supplement"],"language":["eng"],"title":[{"subtitle":"official publication of the American College of Neuropsychopharmacology","title":"Neuropsychopharmacology","title_sort":"Neuropsychopharmacology"}],"disp":"The calpain inhibitor A-705253 attenuates alcohol-seeking and relapse with low side-effect profileNeuropsychopharmacology"}],"recId":"1662464932"} | ||
| SRT | |a VENGELIENECALPAININH2016 | ||