The goal of this research proposal is to examine the mechanisms of retrieval and reconsolidation of memories acquired through learned associations between environmental stimuli and drugs of abuse. In humans, these previously neutral stimuli come to elicit drug-seeking behaviors, even after prolonged abstinence. Thus, characterizing the memory mechanisms mediating the effects of drug-associated stimuli is critical for understanding drug addiction and relapse, and may provide insight into the development of novel pharmacotherapies designed to treat reactivity to drug-related stimuli. Specifically, this project seeks to determine the role of dopamine D1 receptors in the basolateral amygdala of rats in retrieval and post- retrieval memory mechanisms mediating stimulus-induced cocaine-seeking behaviors. Dopamine D1 receptors in the basolateral amygdala have been implicated in the reactivity to cocaine-related stimuli in animal models of relapse. Thus, memories induced by cocaine-stimulus associations are likely mediated, by these receptors. The conditioned place preference paradigm will be used to determine whether re-exposure to a stimulus previously paired with cocaine results in a stimulus-specific increase in gene expression- as measured by c-Fos induction- in the basolateral amygdala. Furthermore, intra-basolateral amygdala microinjection of a dopamine D1 antagonist prior to stimulus re-exposure will be used to determine the role of these receptors in this potential memory retrieval-induced c-Fos expression. The role of dopamine D1 receptors in the amygdala in post-retrieval memory mechanisms will also be examined. Intra-basolateral amygdala microinjection of a dopamine D1 antagonist will be administered immediately following stimulus re-exposure in the conditioned place preference paradigm to determine a role for these receptors in the potential reconsolidation of cocaine-related memories, as assessed during a subsequent test for place preference. These data may provide valuable insight into the memory mechanisms that govern addiction. Identifying the neurobiological mechanisms of memory underlying responses to environmental stimuli paired with drugs of abuse such as cocaine is key to understanding addiction and relapse. The current proposal focuses on a specific brain area known as the amygdala, and its potential role in memory processes that mediate the effects of cocaine-related stimuli and perpetuate addiction. ? ? ?
|Bernardi, Rick E; Lattal, K Matthew (2012) Prazosin differentially affects extinction of cocaine conditioned place preference on the basis of dose and initial preference. Neuroreport 23:1048-51|
|Bernardi, Rick E; Lattal, K Matthew (2012) Post-conditioning propranolol disrupts cocaine sensitization. Pharmacol Biochem Behav 102:515-9|
|Bernardi, Rick E; Lattal, K Matthew (2010) A role for alpha-adrenergic receptors in extinction of conditioned fear and cocaine conditioned place preference. Behav Neurosci 124:204-10|
|Bernardi, Rick E; Lewis, Jason R; Lattal, K Matthew et al. (2009) Modafinil reinstates a cocaine conditioned place preference following extinction in rats. Behav Brain Res 204:250-3|
|Bernardi, Rick E; Ryabinin, Andrey E; Berger, S Paul et al. (2009) Post-retrieval disruption of a cocaine conditioned place preference by systemic and intrabasolateral amygdala beta2- and alpha1-adrenergic antagonists. Learn Mem 16:777-89|
|Lattal, K Matthew; Bernardi, Rick E (2007) Cellular learning theory: theoretical comment on Cole and McNally (2007). Behav Neurosci 121:1140-3|