PMID- 34183434
OWN - NLM
STAT- MEDLINE
DCOM- 20211222
LR  - 20240428
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 378
IP  - 3
DP  - 2021 Sep
TI  - The Buprenorphine Analogue BU10119 Attenuates Drug-Primed and Stress-Induced 
      Cocaine Reinstatement in Mice.
PG  - 287-299
LID - 10.1124/jpet.121.000524 [doi]
AB  - There are no Food and Drug Administration-approved medications for cocaine use 
      disorder, including relapse. The mu-opioid receptor (MOPr) partial agonist 
      buprenorphine alone or in combination with naltrexone has been shown to reduce 
      cocaine-positive urine tests and cocaine seeking in rodents. However, there are 
      concerns over the abuse liability of buprenorphine. Buprenorphine's partial 
      agonist and antagonist activity at the nociception receptor (NOPr) and kappa-opioid 
      receptor (KOPr), respectively, may contribute to its ability to inhibit cocaine 
      seeking. Thus, we hypothesized that a buprenorphine derivative that exhibits 
      antagonist activity at MOPr and KOPr with enhanced agonist activity at the NOPr 
      could provide a more effective treatment. Here we compare the pharmacology of 
      buprenorphine and two analogs, BU10119 and BU12004, in assays for antinociception 
      and for cocaine- and stress-primed reinstatement in the conditioned place 
      preference paradigm. In vitro and in vivo assays showed that BU10119 acts as an 
      antagonist at MOPr, KOPr, and delta-opioid receptor (DOPr) and a partial agonist at 
      NOPr, whereas BU12004 showed MOPr partial agonist activity and DOPr, KOPr, and 
      NOPr antagonism. BU10119 and buprenorphine but not BU12004 lessened 
      cocaine-primed reinstatement. In contrast, BU10119, BU12004, and buprenorphine 
      blocked stress-primed reinstatement. The selective NOPr agonist SCH221510 but not 
      naloxone decreased cocaine-primed reinstatement. Together, these findings are 
      consistent with the concept that NOPr agonism contributes to the ability of 
      BU10119 and buprenorphine to attenuate reinstatement of cocaine-conditioned place 
      preference in mice. The findings support the development of buprenorphine analogs 
      lacking MOPr agonism with increased NOPr agonism for relapse prevention to 
      cocaine addiction. SIGNIFICANCE STATEMENT: There are no Food and Drug 
      Administration-approved medications for cocaine use disorder. Buprenorphine has 
      shown promise as a treatment for cocaine relapse prevention; however, there are 
      concerns over the abuse liability of buprenorphine. Here we show a buprenorphine 
      analogue, BU10119, which lacks mu-opioid receptor agonism and inhibits 
      cocaine-primed and stress-primed reinstatement in a conditioned place-preference 
      paradigm. The results suggest the development of BU10119 for the management of 
      relapse to cocaine seeking.
CI  - Copyright (c) 2021 by The American Society for Pharmacology and Experimental 
      Therapeutics.
FAU - Hillhouse, Todd M
AU  - Hillhouse TM
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.).
FAU - Olson, Keith M
AU  - Olson KM
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.).
FAU - Hallahan, James E
AU  - Hallahan JE
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.).
FAU - Rysztak, Lauren G
AU  - Rysztak LG
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.).
FAU - Sears, Bryan F
AU  - Sears BF
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.).
FAU - Meurice, Claire
AU  - Meurice C
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.).
FAU - Ostovar, Mehrnoosh
AU  - Ostovar M
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.).
FAU - Koppenhaver, Peyton O
AU  - Koppenhaver PO
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.).
FAU - West, Joshua L
AU  - West JL
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.).
FAU - Jutkiewicz, Emily M
AU  - Jutkiewicz EM
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.).
FAU - Husbands, Stephen M
AU  - Husbands SM
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.).
FAU - Traynor, John R
AU  - Traynor JR
AD  - Department of Psychology, University of Wisconsin Green Bay, Green Bay, Wisconsin 
      (T.M.H., P.O.K.); Department of Pharmacology and Edward F. Domino Research 
      Center, University of Michigan Medical School, Ann Arbor, Michigan (K.M.O., 
      J.E.H., L.G.R., B.F.S., C.M., J.W., E.M.J., J.R.T.); Department of Pharmacy and 
      Pharmacology, and Center for Therapeutic Innovation, University of Bath, Bath, 
      United Kingdom (M.O., S.M.H.); and Department of Medicinal Chemistry, College of 
      Pharmacy, University of Michigan, Ann Arbor, Michigan (J.R.T.) 
      jtraynor@umich.edu.
LA  - eng
GR  - R01 DA007315/DA/NIDA NIH HHS/United States
GR  - R37 DA039997/DA/NIDA NIH HHS/United States
GR  - T32 DA007268/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210628
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (OREX-1019)
RN  - 0 (Receptors, Opioid, mu)
RN  - 40D3SCR4GZ (Buprenorphine)
RN  - 5S6W795CQM (Naltrexone)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Buprenorphine
MH  - *Cocaine
MH  - Naltrexone
MH  - Receptors, Opioid, mu
PMC - PMC11047085
EDAT- 2021/06/30 06:00
MHDA- 2021/12/24 06:00
PMCR- 2021/09/01
CRDT- 2021/06/29 05:53
PHST- 2021/01/19 00:00 [received]
PHST- 2021/06/22 00:00 [accepted]
PHST- 2021/06/30 06:00 [pubmed]
PHST- 2021/12/24 06:00 [medline]
PHST- 2021/06/29 05:53 [entrez]
PHST- 2021/09/01 00:00 [pmc-release]
AID - jpet.121.000524 [pii]
AID - JPET_AR2021000524 [pii]
AID - 10.1124/jpet.121.000524 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2021 Sep;378(3):287-299. doi: 10.1124/jpet.121.000524. Epub 
      2021 Jun 28.