Master of Science
Dr. Steven Laviolette
The molecular mechanisms involved in acquiring opiate-related associative memories are largely unknown. One neural region implicated in the formation of opiate-related memories is the basolateral nucleus of the amygdala (BLA). Transmission through dopamine (DA) receptors within the BLA controls the formation of opiate-related reward memories (Lintas et al., 2011; Lintas et al., 2012). Specifically, transmission through DA D1 receptors controls opiate reward memory formation in animals that are previously naïve to opiate exposure. However, once opiate dependence and withdrawal are present, intra-BLA DA-mediated control of opiate reward memory processing switches to a DA D2 receptor substrate. These findings demonstrate a DA receptor D1"D2 functional switching mechanism controlling the acquisition of opiate-related memories. However, it is unclear what are the underlying molecular substrates controlling the transition from a D1 to a D2 receptor-dependent memory mechanism are, and how chronic opiate exposure controls the process. Using a Pavlovian Place Preference (CPP) paradigm combined with molecular protein analyses, we tested the hypothesis that D1 and D2-like receptors in the BLA control the acquisition of opiate reward memory through modulation of intracellular phosphorylated MEK and phosphorylated CaMKII levels, respectively. We report that intra-BLA blockade of MEK inhibits opiate reward memory acquisition in previously opiate-naïve but not opiate dependent/withdrawn animals. Conversely, inhibition of CaMKII phosphorylation blocks the acquisition of opiate-related reward memory only in opiate dependent/withdrawn animals. Furthermore, chronic opiate exposure down-regulates the phosphorylation of MEK, and dramatically down-regulates expression levels of CaMKII. Our findings demonstrate a novel opiate exposure-state dependent molecular switch within the BLA controlling the formation of opiate-related reward memories.
Lyons, Danika C.A., "Identification of a Molecular Opiate-Addiction Memory Switch in the Basolateral Amygdala" (2012). University of Western Ontario - Electronic Thesis and Dissertation Repository. Paper 683.