Molecular and genetic substrates linking stress and addiction

Abstract

Drug addiction is one of the top three health concerns in the United States in terms of economic and health care costs. Despite this, there are very few effective treatment options available. Therefore, understanding the causes and molecular mechanisms underlying the transition from casual drug use to compulsive drug addiction could aid in the development of treatment options. Studies in humans and animal models indicate that stress can lead to both vulnerability to develop addiction, as well as increase drug taking and relapse in addicted individuals. Exposure to stress or drugs of abuse results in long-term adaptations in the brain that are likely to involve persistent alterations in gene expression or activation of transcription factors, such as the cAMP Response Element Binding protein, CREB. The signaling pathways controlled by CREB have been strongly implicated in drug addiction and stress. Many potential CREB target genes have been identified based on the presence of a CRE element in promoter DNA sequences. These include, but are not limited to CRF, BDNF, and dynorphin. These genes have been associated with initiation or reinstatement of drug reward and are altered in one direction or the other following stress. While many reviews have examined the interactions between stress and addiction, the goal of this review is to focus on specific molecules that play key roles in both stress and addiction and are therefore posed to mediate the interaction between the two. Focus on these molecules could provide us with new targets for pharmacological treatments for addiction.

Resveratrol Inhibits the Proliferation of Neural Progenitor Cells and Hippocampal Neurogenesis

“…Indeed, we found that resveratrol can suppress the production of BDNF by neurons, which may contribute to the inhibition of neurogenesis in vivo because BDNF is known to promote the differentiation and survival of hippocampal NPCs (63). The results of our immunostaining with a pCREB antibody suggest that resveratrol causes a reduction in CREB activity which could contribute to reduced neurogenesis because CREB induces the expression of BDNF (64,65). Again, this contrasts with DR which up-regulates CREB (66).…”

Differential regulation of glutamic acid decarboxylase gene expression after extinction of a recent memory vs. intermediate memory

“…Exposure to stress induces long-term adaptations in the brain that involve persistent alterations in gene expression (Briand and Blendy 2010). Most studies investigate how extinction affects a recently formed fear memory, usually administering extinction training 24 h after fear learning.…”

Identification of a Novel Protein Kinase A Inhibitor by Bioluminescence-Based Screening

“…1,2) However, overactivation of CREB is seen in the brain of patients with posttraumatic stress disorder 3) and addiction. 4) Moreover elevated activation of CREB has been demonstrated in some tumor cells. [5][6][7] Thus it is considered that inhibitors of this pathway may be used as medicines for these diseases.…”