MedicalResearch.com Interview with:
Ana-Clara Bobadilla, Ph.D.
in the laboratory of Peter Kalivas, Ph.D
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The Brain-derived neurotrophic factor (BDNF) is a growth factor that has well-described effects in the survival, growth and differentiation of neurons during development of the central nervous system, but it also maintains a role during adulthood in learning, memory and various disorders such as addiction. Several clinical studies show increased BDNF levels in the serum of cocaine- or alcohol-dependent patients compared to controls (D’Sa et al., 2011; D’Sa et al., 2012). In preclinical research, a wealth of studies shows that chronic exposure to drugs of abuse impacts BDNF expression in different parts of the brain, including the main regions comprised in the reward circuitry, the cortex and the nucleus accumbens (for a comprehensive review, see Li & Wolf, 2015). Conversely, altering BDNF expression or transmission has profound effects on the response of the brain to drugs (see McGinty et al., 2010). Importantly, BDNF effects are often region-specific, meaning that an increase in BDNF expression in one region can decrease the effects of drug exposure in the brain while the same increase in another region can have opposite effects (Li et al., 2013). Because BDNF transmission can modify the expression of a wide range of genes leading to long-term modifications, numerous studies administer BDNF early in the drug exposure protocol and focus on the long-term changes induced by the growth factor.
In this study, we microinjected BDNF directly in the nucleus accumbens minutes before measuring cocaine craving in a well-known rodent model of relapse. We found that BDNF induces a robust decrease in craving that lasts for at least 3 days post-treatment. The inhibitory effect of BDNF is not seen when animals are tested for sucrose, a very strong reward for rats, suggesting that this effect is specific to cocaine.
Moreover, cocaine craving is only decreased when BDNF is microinjected before the craving test, but has no effect when injected a day before the craving test or in the home cage, indicating a time-specificity in addition to the region-specificity previously described.
MedicalResearch.com: What should readers take away from your report?
Response: This report characterizes an acute inhibitory role of BDNF on cocaine craving, suggesting BDNF could be a molecule with therapeutic properties. However, many previous studies show that BDNF effects are region-dependent. Because in this study BDNF was administered intracranially in the nucleus accumbens region during a very specific window around the induction of cocaine craving, further research is needed to determine if this inhibitory effect of BDNF could be used to decrease relapse.
The results of this study are an additional piece of the puzzle supplementing the literature and helping the scientific community to understand better the complexity of chronic substance abuse.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: As mentioned above, BDNF injections targeted the nucleus accumbens. In this key region of the reward circuitry, the vast majority of neurons are divided in two categories, based on the type of dopamine receptor they express: the D1 (dopamine receptor type 1) neurons or the D2 neurons. In our report we were unable to dissociate the role of BDNF on these two types of neurons because of technical limitations. However, it has been previously reported that BDNF transmission can be different between D1 and D2 neurons (Lobo et al., 2010). The next step in our research is to determine by what cell-specific mechanism does BDNF transmission inhibit cocaine craving when administered immediately before a test.
MedicalResearch.com: Is there anything else you would like to add?
Response: This work was funded by an international post-doctoral fellowship from the French Fyssen Foundation (ACB) and the National Institute on Drug Abuse (PWK).
Ana-Clara Bobadilla, Constanza Garcia-Keller, Victoria Chareunsouk, Jeffrey Hyde, Daniela Medina Camacho, Jasper A. Heinsbroek, Peter W. Kalivas. Accumbens brain-derived neurotrophic factor (BDNF) transmission inhibits cocaine seeking. Addiction Biology, 2018; DOI: 10.1111/adb.12638
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