Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wistar rats

Rationale Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction. Materials and methods We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chl...

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Published inPsychopharmacologia Vol. 211; no. 4; pp. 367 - 375
Main Authors Cippitelli, Andrea, Karlsson, Camilla, Shaw, Janice L., Thorsell, Annika, Gehlert, Donald R., Heilig, Markus
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer-Verlag 01.09.2010
Springer
Springer Nature B.V
Subjects
Alcohol
Alcohol Drinking - prevention & control
Animal behavior
Animals
Anti-Obesity Agents - administration & dosage
Anti-Obesity Agents - pharmacology
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Dose-Response Relationship, Drug
Drug addictions
Drug Delivery Systems
Footshock
Hormones
Male
MCH1-R
Medical sciences
Miscellaneous
Motor Activity - drug effects
Neurosciences
Original Investigation
Pharmacology. Drug treatments
Pharmacology/Toxicology
Psychiatry
Psychopharmacology
Pyrimidinones - administration & dosage
Pyrimidinones - pharmacology
Rats
Rats, Wistar
Receptors, Somatostatin - antagonists & inhibitors
Reinstatement
Reward
Rodents
Saccharin
Secondary Prevention
Seeking
Self Administration
Taste - drug effects
Thiophenes - administration & dosage
Thiophenes - pharmacology
Toxicology
Footshock
Alcohol
Saccharin
MCH1-R
Seeking
Reinstatement
Affect affectivity
Rat
Rodentia
Emotion emotionality
Self administration
Experimental study
Alcoholic beverage
Vertebrata
Mammalia
Animal
Melanin concentrating hormone
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Abstract Rationale Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction. Materials and methods We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3 H -thieno[3,2- d ]pyrimidin-4-one; 3–30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats. Results Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected. Conclusion Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.
AbstractList RATIONALE: Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction. MATERIALS AND METHODS: We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one; 3-30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats. RESULTS: Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected. CONCLUSION: Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.
Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction. We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one; 3-30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats. Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected. Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.[PUBLICATION ABSTRACT]
Rationale: Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction. Materials and methods: We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phe n yl]-3H-thieno[3,2-d]pyrimidin-4-on e; 3-30mg/kg, i.p.] on alcohol-related behaviors in Wistar rats. Results: Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected. Conclusion: Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.
Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction. We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one; 3-30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats. Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected. Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.
Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction.RATIONALEMelanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction.We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one; 3-30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats.MATERIALS AND METHODSWe evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one; 3-30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats.Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected.RESULTSEx vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected.Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.CONCLUSIONTogether, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.
Rationale Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction. Materials and methods We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3 H -thieno[3,2- d ]pyrimidin-4-one; 3–30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats. Results Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected. Conclusion Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.
Author Gehlert, Donald R.
Cippitelli, Andrea
Heilig, Markus
Karlsson, Camilla
Shaw, Janice L.
Thorsell, Annika
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  givenname: Camilla
  surname: Karlsson
  fullname: Karlsson, Camilla
  organization: Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH)
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  givenname: Janice L.
  surname: Shaw
  fullname: Shaw, Janice L.
  organization: Neuroscience and Endocrine Discovery Research, Lilly Research Laboratories, a Division of Eli Lilly and Company
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  givenname: Annika
  surname: Thorsell
  fullname: Thorsell, Annika
  organization: Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH)
– sequence: 5
  givenname: Donald R.
  surname: Gehlert
  fullname: Gehlert, Donald R.
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  givenname: Markus
  surname: Heilig
  fullname: Heilig, Markus
  email: markus.heilig@mail.nih.gov
  organization: Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH)
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IEDL.DBID 7X7
ISSN 0033-3158
1432-2072
IngestDate Thu Aug 21 07:06:49 EDT 2025
Thu Jul 10 16:49:27 EDT 2025
Fri Jul 11 03:43:57 EDT 2025
Sat Aug 16 22:21:54 EDT 2025
Wed Feb 19 02:30:56 EST 2025
Wed Apr 02 07:26:53 EDT 2025
Thu Apr 24 23:08:41 EDT 2025
Sun Jul 06 05:07:35 EDT 2025
Fri Feb 21 02:34:21 EST 2025
IsPeerReviewed true
IsScholarly true
Issue 4
Keywords Footshock
Alcohol
Saccharin
MCH1-R
Seeking
Reinstatement
Affect affectivity
Rat
Rodentia
Emotion emotionality
Self administration
Experimental study
Alcoholic beverage
Vertebrata
Mammalia
Animal
Melanin concentrating hormone
Language English
License http://www.springer.com/tdm
CC BY 4.0
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MergedId FETCHMERGED-LOGICAL-c470t-4f054fe991cfd0d692b3c66fd57ce2064dcfd57a959d1f00a0f97d301fbff4543
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content type line 23
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PQID 722692227
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proquest_miscellaneous_734008343
proquest_journals_722692227
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pascalfrancis_primary_23066889
crossref_primary_10_1007_s00213_010_1891_y
crossref_citationtrail_10_1007_s00213_010_1891_y
springer_journals_10_1007_s00213_010_1891_y
PublicationCentury 2000
PublicationDate 2010-09-01
PublicationDateYYYYMMDD 2010-09-01
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  year: 2010
  text: 2010-09-01
  day: 01
PublicationDecade 2010
PublicationPlace Berlin/Heidelberg
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PublicationTitle Psychopharmacologia
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PublicationYear 2010
Publisher Springer-Verlag
Springer
Springer Nature B.V
Publisher_xml – name: Springer-Verlag
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Snippet Rationale Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains...
Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant...
Rationale: Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains...
RATIONALE: Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains...
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pubmed
pascalfrancis
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SourceType Open Access Repository
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Index Database
Enrichment Source
Publisher
StartPage 367
SubjectTerms Alcohol
Alcohol Drinking - prevention & control
Animal behavior
Animals
Anti-Obesity Agents - administration & dosage
Anti-Obesity Agents - pharmacology
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Dose-Response Relationship, Drug
Drug addictions
Drug Delivery Systems
Footshock
Hormones
Male
MCH1-R
Medical sciences
Miscellaneous
Motor Activity - drug effects
Neurosciences
Original Investigation
Pharmacology. Drug treatments
Pharmacology/Toxicology
Psychiatry
Psychopharmacology
Pyrimidinones - administration & dosage
Pyrimidinones - pharmacology
Rats
Rats, Wistar
Receptors, Somatostatin - antagonists & inhibitors
Reinstatement
Reward
Rodents
Saccharin
Secondary Prevention
Seeking
Self Administration
Taste - drug effects
Thiophenes - administration & dosage
Thiophenes - pharmacology
Toxicology
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Title Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wistar rats
URI https://link.springer.com/article/10.1007/s00213-010-1891-y
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