Scientists identify how repeated cocaine use increases the addictiveness

The brain structures are responsible for compulsive drug-seeking behaviors due to repeated use of cocaine.


Millions of people are struggling with cocaine addiction, a neurobiological disorder caused by repeated drug use. It changes the reward and adaptive behavior pathways in the brain and body. A Scientific team is breaking barriers to determine the leading cause of cocaine addiction. They also find solutions for those struggling and needing help.  

The Federal University of São Paulo, Brazil, and the University of Bristol Veterinary School, UK, have identified the brain structures responsible for compulsive drug-seeking behaviors due to repeated use of cocaine.

These findings show that repeated use of cocaine leads to connect learning, so an individual associates the euphoric effect promoted by the drug with the environment where it is used. As a result, a reinforcing system is established, meaning that two stimuli will be connected with choice or compulsive desire for the drug. Therefore, the environment plays a key role in activating and expressing behavioral responses to cocaine.

These findings are published in Biomedicines and identify the structures involved and neural pathways activated with repeated exposure to the drug. Researchers hope the study could help inform treatment for drug addiction.

Research showed brain structures involved in response to cocaine. Scientists believe it supports compulsive desire for the drug by changing areas of the brain’s neural pathways that regulate reward & adaptive behaviors.

Animal models and an innovative state-of-the-art 3D quantitative image analysis process, stereology, were used to identify brain structures activated upon repeated cocaine exposure.

The study shows that the dorsomedial prefrontal cortex (dmPFC), nucleus accumbens (NAc) core, and basolateral amygdala (BLA) of the brain all play a role during both induction and expression of behavioral reactions to cocaine. In contrast, the ventral tegmental area (VTA’s) is more involved only at the induction point.

Professor Beatriz Longo from the Federal University of São Paulo, the lead author of this study, Dr. Renan Baldaia, the first author of the article, and Dr. Augusto Coppi, a world leader in 3D quantitative image analysis and Lecturer in Veterinary Clinical Anatomy at the University of Bristol, said: “Understanding behavioral changes involved in drug addiction, as well as identifying the brain structures involved in such behaviors in animal models, opens up possibilities for new therapeutic tools and interventions in the management of drug addiction.”

The team looks forward to furthering their research in determining the brain structures related to behavioral responses to other drugs, such as alcohol, marijuana, and nicotine.

The study was funded by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) in Brazil.

Some limitations of their research were that they could not select to decide the estrous cycle of females due to the stress created by the vaginal smear. Instead of monitoring the process, they used a heterogeneous population of female mice, generating robust statistical data indicating significant differences based on heterogeneity. 

Other limitations concern the sensibility of c-Fos antibodies to different stimuli and difficulties in standardizing stereological parameters. All limitations identified in this study should be addressed in future studies.

Their results showed that in the induction phase of cocaine conditioning, the animals that received cocaine paired with the open field presented a significant increase in locomotor activity compared to the control, which characterizes the development of behavioral sensitization.

This research has an essential effect on understanding and treating addiction and developing strategies to prevent people from using cocaine.

Journal Reference:

  1. Viviam Sanabria, Raphael Wuo-Silva et al. Distinctive Neuroanatomic Regions Involved in Cocaine-Induced Behavioral Sensitization in Mice. Biomedicines. DOI: 10.3390/biomedicines11020383
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