Marchigian Sardinian Alcohol-Preferring (msP) rats were genetically selected and bred for alcohol drinking. msP rats also inherit anxiety-like behavior.
These negative behavioral outcomes are largely associated with disrupted glucocorticoid signaling in msP rats, which is related to genetic alterations of corticotropin-releasing factor receptor 1 (CRF1) inherited in msPs rats. As a result, msPs served as a model to study pharmacological interventions that target glucocorticoid signaling regarding alcohol and stress vulnerability.
Recent work has shed light on the strong efficacy of mifepristone, a glucocorticoid receptor antagonist to reduce alcohol drinking in humans and rodents. However, mifepristone’s efficacy on stress and anxiety-like behaviors remains poorly understood.
Vozella and Cruz et al (2021) showed that mifepristone (60mg/kg) did not reduce heightened stress responses and anxiety-like behavior in msPs versus normal control rats. With collaborators from the University of Camerino, Italy, Vozella and Cruz co-authored work which demonstrated that mifepristone did not reduce alcohol drinking in msPs rats, but reliably reduce alcohol drinking in normal control rats (Benvenuti et al 2021).
These results suggest that msP rats might have a distinct regulation of the glucocorticoid signaling and negative feedback processes that work to normalize stress which may impact the effectiveness of mifepristone administration. This work provides information about genetically inheritable enhanced alcohol drinking and stress vulnerability.
Glucocorticoid Receptor Antagonist Mifepristone Does Not Alter Innate Anxiety-Like Behavior in Genetically-Selected Marchigian Sardinian (msP) Rats.
Vozella V*, Cruz B*, Natividad LA, Benvenuti F, Cannella N, Edwards S, Zorrilla EP, Ciccocioppo R, Roberto M.
Effect of Glucocorticoid Receptor Antagonism on Alcohol Self-Administration in Genetically-Selected Marchigian Sardinian Alcohol-Preferring and Non-Preferring Wistar Rats.
Benvenuti F, Cannella N, Stopponi S, Soverchia L, Ubaldi M, Lunerti V, Vozella V, Cruz B, Roberto M, Ciccocioppo R.