DEVELOPMENT OF A TRANSLATIONAL MODEL OF CO-USE OF ALCOHOL AND NICOTINE FOR TESTING POTENTIAL PHARMACOTHERAPIES
Year of Publication
Doctor of Philosophy (PhD)
Arts and Sciences
Dr. Michael Bardo
Co-users of alcohol and nicotine are the largest group of polysubstance users worldwide. Although pharmacotherapies are available for alcohol (EtOH) or tobacco use disorders individually, it may be possible to develop a single pharmacotherapy to treat heavy drinking tobacco smokers through capitalizing on the commonalities in their mechanisms of action. Towards this goal, several models of concurrent access to EtOH and nicotine were explored as potential preclinical models of co-use using female alcohol-preferring (P) rats. Additionally, potential pharmacotherapeutics for the treatment of EtOH and nicotine co-use disorder were tested using different variations of our model. Treatments tested included (1) varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist with high affinity for the α4β2* subtype; (2) r-bPiDI, a subtype-selective antagonist at α6β2* nAChRs; (3) (R)-modafinil, an atypical inhibitor of the dopamine transporter (DAT); and (4) naltrexone, a clinically available µ-opioid receptor antagonist used to treat alcohol use disorder (AUD).
Results from the current dissertation show success in developing a translational animal model in female P rats for co-use of EtOH and nicotine under which pharmacologically relevant levels of both EtOH consumption and nicotine intake are achieved. Additionally, our model was successfully used in testing potential pharmacotherapeutics for the treatment of EtOH and nicotine co-use disorder. Although none of the drugs tested were effective as a monotherapy, results from testing the known smoking cessation agent varenicline and the known AUD treatment naltrexone indicate that our model is effective for selectively measuring changes in EtOH and nicotine intake separately, which suggests the beneficial utility of this model for future treatment research.
Furthermore, by applying behavioral economic principles to our findings, we found that EtOH acts as an economic substitute for nicotine. Additionally, our behavioral economic analyses revealed that when the cost of nicotine is changed via response requirements vs dose per infusion, there are differences in the elasticity of demand for concurrently available EtOH and nicotine. Finally, the relatively flat consumption curve for EtOH following varenicline pretreatment suggests that pretreatment with varenicline acts to disrupt the relationship between EtOH and nicotine such that EtOH no longer acts as an economic substitute for nicotine.
Digital Object Identifier (DOI)
The Lipman Award for alcohol research T32 DA016176 R01 AA025591.
Maggio, Sarah Elizabeth, "DEVELOPMENT OF A TRANSLATIONAL MODEL OF CO-USE OF ALCOHOL AND NICOTINE FOR TESTING POTENTIAL PHARMACOTHERAPIES" (2019). Theses and Dissertations--Psychology. 167.