Understanding the Impact of Chronic Stress in Cocaine Addiction: How Stress influences the Behavior and Biology of Addiction?

Cocaine addiction is a chronic relapsing disorder influenced by both neurobiological and environmental factors, including stress. This study investigated the impact of stress-induced corticosterone elevation on the expression of key dopaminergic signaling components involved in cocaine reward: dopamine receptors D1 and D2, dopamine transporter (DAT), and protein kinase A (PKA) in a rat model. Using a conditioned place preference (CPP) paradigm, male rats were divided into four groups: non-stressed control, stressed control, non-stressed CPP, and stressed CPP. Stress was induced using 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a predator odor. Following behavioral testing, nucleus accumbens (NAc) tissue was collected from each side of the brain with one hemisphere analyzed by quantitative PCR and the other reserved for protein-level analysis. PCR results revealed a marked increase in D1 receptor mRNA expression in the stressed groups, with the stressed CPP group exhibiting the highest levels, however, this change was not statistically significant. D2 receptor expression, on the other hand, showed lower expression in the stressed-cocaine group compared to stressed or-unstressed control. DAT and PKA expressions did not follow a consistent pattern. Coomassie staining was performed to assess protein levels but did not show specificity among proteins D1, D2 and DAT. These findings suggest that stress may potentiate the neurobiological response to cocaine by changing the expression of receptors in the dopamine pathway.