V1b Receptor Antagonist SSR149415 and Naltrexone Synergistically Decrease Excessive Alcohol Drinking in Male and...

Area of Science:

• Neuroscience
• Pharmacology
• Addiction Research

Background:

• Pharmacological blockade of V1b receptors shows promise in reducing alcohol relapse.
• SSR149415 is a selective V1b receptor antagonist with potential for alcohol dependency treatment.
• Investigating SSR149415 alone and with mu-opioid receptor (MOP-r) antagonist naltrexone (NTN) for alcohol drinking reduction.

Purpose of the Study:

• To evaluate the efficacy of SSR149415 in reducing excessive alcohol consumption in mice.
• To determine if SSR149415 and naltrexone (NTN) exhibit synergistic effects in reducing alcohol intake.
• To explore the potential of combined V1b and MOP-r antagonism for alcoholism treatment.

Main Methods:

• Utilized a chronic intermittent access (IA) drinking paradigm in male and female C57BL/6J (B6) mice.
• Employed sucrose and saccharin as control solutions to assess alcohol-specific effects.
• Used neuronal proopiomelanocortin (POMC) enhancer (nPE) knockout mice to control for NTN's effects.

Main Results:

• SSR149415 administration dose-dependently reduced alcohol intake and preference in both sexes.
• A combination of SSR149415 (3 mg/kg) and NTN (1 mg/kg) profoundly reduced alcohol intake at sub-effective individual doses.
• SSR149415's effect on alcohol intake was confirmed in nPE-/- mice, indicating independent mechanisms from NTN.

Conclusions:

• Combination therapy of SSR149415 and NTN at subthreshold doses shows significant potential for treating alcoholism.
• This combined approach may offer a more effective treatment strategy with potentially fewer adverse effects.
• The findings support further investigation into V1b receptor antagonists and MOP-r antagonists for alcohol use disorder therapies.