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Louisiana Biomedical Research Network

Erika Perez

Link to Pubmed Publications

Xavier University of Louisiana


Project Title

The interaction between kainate (KRs) and nicotinic acetylcholine receptors (nAChRs) in modulating nicotine-associated behaviors.



Funding Period

Startup Project (May 1, 2021 - April 30, 2023)


Abstract


Clinical studies looking at the use of the antiepileptic drug, Topiramate, to treat alcoholics have found that tobacco smoking behaviors are significantly reduced. Up to this point only a couple studies have been done to model these effects in pre-clinical rodent models as it relates to nicotine dependence. The main goal of this proposal is to characterize the impact that GluK1-containing kainate receptors (GluK1*KARs) have in modulating nicotine withdrawal symptoms. GluK*1KARS are non-selectively inhibited by topiratmate and genetic association studies suggest that this receptor system could be targeted to reduce drinking in AUD patients. My post doctoral work highlighted the role of GluK1*KARs in the manifestations of physical symptoms of alcohol withdrawal. My previous work also established that nicotinic acetylcholine (nAChRs) within the interpeduncular nucleus (IPN) play a role in the modulation of these physical signs of withdrawal from nicotine, alcohol and both drugs concurrently. To date the connection between these two receptor types has not been explored. Aim 1 of this proposal will address the hypothesis that Topiramate and a more selective GluK1*KARs antagonist is sufficient to reduce both affective and physical symptoms of nicotine withdrawal. Both antagonists will be administered in animals undergoing 24 hr nicotine cessation before being tested for nicotine withdrawal-induced anxiety-like behavior, depression-like behavior, cognitive inflexibility, hyperalgesia and somatic signs. Aim 1 will also address whether GluK1*KARs within the basal lateral amygdala (BLA) can reduce nicotine withdrawal symptoms. Aim 2 will characterize the neuronal connection between the IPN and BLA in modulating nicotine withdrawal symptoms. Using both pharmacological and genetic techniques we will investigate the nature of these connections, whether they are within the same circuit or working in parallel neuronal circuits