Tag: cocaine use

Continued Cocaine Use Disrupts Communication between Major Brain Networks

Photo by Colin Davis on Unsplash

A collaborative research endeavour by scientists in the Departments of Radiology, Neurology, and Psychology and Neuroscience at the UNC School of Medicine have demonstrated the deleterious effects of chronic cocaine use on the functional networks in the brain.

Their study titled “Network Connectivity Changes Following Long-Term Cocaine Use and Abstinence,” was highlighted by the editor of Journal of Neuroscience in “This Week in The Journal.” The findings show that continued cocaine use affects how crucial neural networks communicate with one another in the brain, including the default mode network (DMN), the salience network (SN), and the lateral cortical network (LCN).

“The disrupted communication between the DMN and SN can make it harder to focus, control impulses, or feel motivated without the drug,” said Li-Ming Hsu, PhD, assistant professor of radiology and lead author on the study. “Essentially, these changes can impact how well they respond to everyday situations, making recovery and resisting cravings more challenging.”

Hsu led this project during his postdoctoral tenure at the Center for Animal MRI in the Biomedical Research Imaging Center and the Department of Neurology. The work provides new insights into the brain processes that underlie cocaine addiction and creates opportunities for the development of therapeutic approaches and the identification of an imaging marker for cocaine use disorders.

The brain operates like an orchestra, where each instrumentalist has a special role crucial for creating a coherent piece of music. Specific parts of the brain need to work together to complete a task. The DMN is active during daydreams and reflections, the SN is crucial for attentiveness, and the CEN, much like a musical conductor, plays a role in our decision-making and problem-solving.

The research was motivated by observations from human functional brain imaging studies suggesting chronic cocaine use alters connectivity within and between the major brain networks. Researchers needed a longitudinal animal model to understand the relationship between brain connectivity and the development of cocaine dependence, as well as changes during abstinence.

Researchers employed a rat model to mimic human addiction patterns, allowing the models to self-dose by nose poke. Paired with advanced neuroimaging techniques, the behavioural approach enables a deeper understanding of the brain’s adaptation to prolonged drug use and highlights how addictive substances can alter the functioning of critical brain networks.

Hsu’s research team used functional MRI scans to explore the changes in brain network dynamics on models that self-administrated cocaine. Over a period of 10 days followed by abstinence, researchers observed significant alterations in network communication, particularly between the DMN and SN.

These changes were more pronounced with increased cocaine intake over the 10 days of self-administration, suggesting a potential target for reducing cocaine cravings and aiding those in recovery. The changes in these networks’ communication could also serve as useful imaging biomarkers for cocaine addiction.

The study also offered novel insights into the anterior insular cortex (AI) and retrosplenial cortex (RSC). The former is responsible for emotional and social processing; whereas, the latter controls episodic memory, navigation, and imagining future events. Researchers noted that there was a difference in coactivity between these two regions before and after cocaine intake. This circuit could be a potential target for modulating associated behavioural changes in cocaine use disorders.

“Prior studies have demonstrated functional connectivity changes with cocaine exposure; however, the detailed longitudinal analysis of specific brain network changes, especially between the anterior insular cortex (AI) and retrosplenial cortex (RSC), before and after cocaine self-administration, and following extended abstinence, provides new insights,” said Hsu.

Source: University of North Carolina Health Care

Single Pathway Controls Drug Withdrawal-induced Anxiety

Depression, young man
Source: Andrew Neel on Unsplash

New research published today in Cell Reports finds that drug withdrawal-induced anxiety and return to drug seeking behaviours are controlled by a single pathway in the brain and are centred on dopamine cells, which are normally associated with reward behaviours.

Addiction occurs in phases: the initial drug exposures are rewarding, and then repeated administration leads to tolerance or sensitisation to the drug’s effects, with withdrawal leading to anxiety and a negative affective state, which, in turn, contributes to a return to drug taking or seeking.

“In order to prevent relapse among drug users, specifically cocaine users, we need to understand the factors in the brain that contribute to drug seeking behaviours and the vulnerability to relapse,” said Kevin Beier, PhD, assistant professor of physiology and biophysics from the University of California, Irvine. “In this study, we identified a brain circuit that is responsible for drug withdrawal-induced anxiety as well as relapse-related behaviour, along with the identification of a potential target for therapeutic interventions.”

The negative affective state induced by drug withdrawal is a critical factor in the relapse of drug users.

“Both the drug withdrawal-induced anxiety and reinstatement of drug seeking are controlled by a single pathway centred around dopamine cells in the ventral midbrain,” explained Dr Beier. “That a single pathway controls both sets of behavioural changes may help to explain many addiction-related behavioural phenomena. Importantly, it links them both directly to dopamine, which is more typically linked to reward-related behaviours.”

While midbrain dopamine circuits are central to motivated behaviours, just how experience modifies these circuits to facilitate subsequent behavioural adaptations is not well understood. This study demonstrates the selective role of a ventral tegmental area dopamine projection to the amygdala for cocaine induced anxiety, but not for cocaine reward or sensitisation. Silencing this projection prevents development of anxiety during protracted withdrawal after cocaine use.

According to the National Center for Drug Abuse Statistics, there are roughly 70 000 drug overdoses each year in the United States. In 2017, nearly one in five drug overdose deaths was cocaine-related, with the highest rate of cocaine-related overdoses and deaths occurring among non-Hispanic black populations. Between 2012 and 2018, the rate of cocaine-related overdose deaths increased from 1.4 to 4.5%. The American Addiction Centers state recent drug relapse statistics show that more than 85% of individuals relapse and return to drug use within a year following treatment.

Source: University of California – Irvine