Pharmacological inhibition of FK506-binding protein 51 reduces alcohol consumption and conditioned place preference in mice

Introduction:

Alcohol addiction is a major psychiatric disorder with no widely effective pharmacotherapy available. The FK506-binding protein 51 (FKBP51) is a negative regulator of the glucocorticoid receptor signaling pathway where it controls a stress-induced glucocorticoid feedback circuit.

Methods:

In this study we investigated how SAFit2, the first selective inhibitor of FKBP51 affects alcohol consumption and conditioned alcohol effects in a mouse model.

Results:

We found that short treatment with SAFit2 (20 mg/kg, i.p.) reduces a previously established 16 vol.% alcohol consumption when administered during free access to alcohol in a two-bottle free-choice test. It also reduced alcohol consumption when given during an abstinence period immediately before relapse. SAFit2 did not affect alcohol consumption when given during a relapse period after repeated withdrawal from alcohol or in an intermittent drinking schedule. SAFit2 (2 and 20 mg/kg, i.p.) did not affect the expression of an alcohol-induced conditioned place preference (CPP) in mice. However, SAFit2 was able to inhibit the alcohol-induced reinstatement of a previously extinguished CPP in a dose-dependent manner.

Conclusion:

These data suggest the pharmacological inhibition of FKBP51 as a potential new strategy to treat alcohol addiction related behaviors.