Experimental Injection Reduces Cocaine Craving

MedicalResearch.com Interview with:

Ana-Clara Bobadilla, Ph.D. Postdoctoral scholar in the laboratory of Peter Kalivas, Ph.D MUSC  Photo by Sarah Pack Medical University of South Carolina

Dr. Ana-Clara Bobadilla (Sarah Pack, photographer)

Ana-Clara Bobadilla, Ph.D.
Postdoctoral scholar
in the laboratory of Peter Kalivas, Ph.D
MUSC 

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.  Continue reading

Bariatric Surgical Approach To Increase Bile Acids May Reduce Cocaine Reward

MedicalResearch.com Interview with:

Aurelio Galli, Ph.D. Professor of Molecular Physiology & Biophysics and Psychiatry & Behavioral Science Associate Director for Research Strategy Vanderbilt Brain Institute

Dr. Galli

Aurelio Galli, Ph.D.
Professor of Molecular Physiology & Biophysics and Psychiatry & Behavioral Science
Associate Director for Research Strategy
Vanderbilt Brain Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The study builds on evidence that bile acids influence the brain’s reward system. Bile acids are normally released from the gall bladder into the upper part of the small intestine, where they emulsify fats for absorption, before being recycled further down the small intestine. In bile diversion surgery, an experimental treatment for weight loss, bile is released at the end of the small intestine, increasing the amount of bile acids that enter the general circulation.

Mice treated with this surgery have less appetite for high-fat foods, which suggests that bile acids affect brain reward pathways.

We demonstrated that mice receiving the surgery also showed less preference for the cocaine-associated chamber, indicating that cocaine was probably less rewarding. Continue reading

Gene Deficit May Give Immunity to Effects of Cocaine

MedicalResearch.com Interview with:
“Cocaine concealed in washing powder” by The National Crime Agency is licensed under CC BY 2.0

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Drug addiction is a chronically relapsing neuropsychiatric disease that affects 15.5 million people in Europe at a cost of 65.7 billion euros per year. All addictive drugs have in common to cause an artificial increase in the release of a neurotransmitter called dopamine, a very basic effect that can be found in all studied animal species from the fly to the man. The release of dopamine takes place in a region of the brain called the ventral striatum, or Nucleus Accumbens (NAc), which is directly involved in reward and reinforcement processes. An excess of dopamine release by the dopaminergic neurons projecting to the NAc from the Ventral Tegmental Area (VTA) triggers long-term changes in the brain, which can lead to addiction.

Cocaine is a prototypical addictive drug, since it is heavely abused in Western societies and extensively studied in animal models as well as humans.

We discovered that mice lacking the Maged1 gene showed a marked decrease in cocaine-elicited release of dopamine in the NAc and were entirely unresponsive to cocaine at behavioral level. In fact, they did not show any behavioral reaction normally observed after cocaine treatment, such as cocaine-elicited hyperlocomotion, sensitization (an increased effect of the drug following repeated administrations) or addictive behaviors, such as increased preference for places where the animal expects to obtain a cocaine reward or cocaine self-administration.

In a subsequent set of experiments, the researchers tried to identify what brain regions are responsible for Maged1 influence on cocaine effects and found that Maged1 expression is specifically required in the prefrontal cortex, and not in the neurons producing dopamine in the VTA, for the development of cocaine sensitization and dopamine release.  Continue reading

Mitochondrial Link To Cocaine Addiction Explored

“cocaine photo” by Imagens Evangélicas is licensed under CC BY 2.0MedicalResearch.com Interview with:
Mary Kay Lobo, PhD

Associate Professor
University of Maryland School of Medicine
Department of Anatomy and Neurobiology
Baltimore, MD 21201 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Altered energy balance has been studied in drug abuse but the fundamental source of energy, mitochondria, has not been well examined.  In this study we found that a molecular regulator of mitochondrial fission (division) is increased in the nucleus accumbens, a major brain reward region, of rodents exposed to repeated cocaine and postmortem samples of cocaine dependent individuals.  We further found that mitochondrial fission is increased in a nucleus accumbens neuron subtype in rodents that self-administer cocaine. Pharmacological blockade of mitochondrial fission can prevent physiological responses to cocaine in this neuron subtype while reducing cocaine-mediated behaviors.  Finally, genetic reduction of mitochondrial fission in this neuron subtype in the nucleus accumbens can reduce drug (cocaine) seeking in rodents previously exposed to cocaine. In contrast, increasing mitochondrial fission, in this neuron subtype, enhances cocaine seeking behavior.

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Cocaine Overdoses Rising Especially Among African Americans

MedicalResearch.com Interview with:
“Cocaine” by Nightlife Of Revelry is licensed under CC BY 2.0Dr. Dave Thomas PhD

Health Scientist Administrator
National Institute on Drug Abuse 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: At the National Institute on Drug Abuse, we support research on all forms of drug use, and are aware that cocaine misuse is on the rise.  We are aware that various forms of drug use can have greater prevalence by race, sex, age and other population characteristics.

The main finding of this paper is that cocaine overdose rates are on the rise and that that the group hit hardest is the non-Hispanic black population.

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Recreational Cocaine Use Activates Addiction Related Brain Mechanisms Sooner Than Previously Realized

MedicalResearch.com Interview with:

Marco Leyton, Ph.D. Professor, Department of Psychiatry McGill University

Dr. Marco Leyton

Marco Leyton, Ph.D.
Professor, Department of Psychiatry
McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Drug-related cues are potent triggers for eliciting conscious and unconscious desire for the drug. In people with severe substance use disorders, these cues also activate dopamine release in the dorsal striatum, a brain region thought to be involved in hard-to-break habits and compulsions.

In the present study we found evidence that drug cues also activate this same dopamine response in non-dependent ‘recreational’ cocaine users.

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Cancer Drug May Mitigate Compulsive Cocaine Memories

MedicalResearch.com Interview with:
Dr Stefania Fasano
Cardiff University

MedicalResearch.com: What is the background for this study?

Response: Exposure to drugs of abuse such as cocaine produces intense and long-lasting memories that are critical in the transition from recreational drug-taking to uncontrolled drug use. In the brain, addictive drugs usurp cellular circuits and signalling molecules involved in normal memory processes; hence, these drug-related memories resist extinction and contribute to high rates of relapse. Despite almost five decades of experimental research, there are currently no approved medications for cocaine dependence.

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Cocaine Chief Cause of Cardiovascular Death In Young People

MedicalResearch.com Interview with:
Luis F. Callado M.D., Ph.D.
Department of Pharmacology
University of the Basque Country
CIBERSAM

Medical Research: What is the background for this study? What are the main findings?

Dr. Callado: Cocaine is the most commonly used illicit stimulant drug in Europe. The use of cocaine has become a major issue for drug policy, with also important health implications, including potentially lethal cardiovascular complications. In this way, several case series have suggested a relationship between cocaine use and cardiovascular diseases in young adults. Furthermore, cocaine use has been also associated with sudden and unexpected death.

Our results demonstrate that the recent use of cocaine is the main risk factor for sudden cardiovascular death in persons between 15 and 49 years old. Thus, persons that consumed cocaine recently presented a 4 times higher risk for sudden cardiovascular death than those who did not use cocaine. The morphological substrate of sudden cardiovascular death associated to cocaine use is a structural pathology not diagnosed in life. Usually, sudden death is the first manifestation of the disease.

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Cocaine: Brain Reward Circuitry Altered, even in Former Users

MedicalResearch.com Interview with:
Krishna Patel, M.S.
Clinical Data Analyst
Hartford Hospital|Institute of Living
Olin Neuropsychiatry Research Center
Hartford, CT-06106

MedicalResearch.com: What are the main findings of the study?

Answer:  We looked at brain response to a monetary incentive delay (MID) task in current and former cocaine users compared to healthy controls using functional MRI. The task measures aspects of sensitivity to rewards and punishments. Current cocaine users showed abnormal under-activation in reward circuitry compared to healthy controls. In some of those regions former cocaine users (who had an average of 4years of abstinence from cocaine) also showed abnormalities. These former users also showed over-activation in the ventral tegmental area of the midbrain, (an important region containing dopamine cell bodies) compared to both healthy controls and current cocaine users. Current and former cocaine users also scored higher on specific impulsivity measures, compared to healthy controls.
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