NEW DELHI, May 13:
Researchers have identified that excitable activity of pyramidal neurons in the decision-making centre of the brain following abstinence from heroin, a commonly used opioid, contributed to relapsing into drug seeking in a rodent model.
They also found that blocking the enzyme protein kinase A (PKA) restored the excitable brain activity following abstinence, along with reducing opioid-seeking behaviour.
The team of neuroscientists at the Medical University of South Carolina (MUSC), US, have published their findings in the Journal of Neuroscience.
“Currently, we lack a comprehensive understanding of the effects of opioids, like heroin, on the neurons that drive return to use. Better understanding these changes may lead to additional treatment options,” said Saurabh Kokane, a postdoctoral scholar at the university.
Substance use disorders are chronic, treatable conditions from which people can recover. These disorders are defined in part by the continued use of substances, despite negative consequences, as well as periods of abstinence followed by a return to use, or relapse. “The challenges with compulsive drug use are the loss of the ability to decide between different behavioural options and the lack of resistance to environmental stimuli that remind you of taking an opioid like heroin,” said Jacqueline McGinty, professor of neuroscience at the university.
The research team found that specific types of pyramidal neurons in the prelimbic prefrontal cortex, a brain region involved in decision-making and behavioral control, undergo molecular and functional changes during abstinence from heroin disrupting normal function in this brain region.
In someone with opioid use disorder, this interference can lead to compulsive drug seeking.
In this study, Kokane and colleagues focused on two of the brain regions responsible for cue-induced relapse, or relapse induced upon encountering a “cue” or “trigger”: the nucleus accumbens and the prelimbic cortex.
“The nucleus accumbens is a brain area that receives input from the prelimbic cortex and from dopamine-releasing pathways that cause the desire to take the substance again that is associated with all addictive drugs, including opioids,” explained Kokane.
During abstinence, aberrant functioning of these pathways is a major contributor to cue-induced relapse.
Through its connections with the nucleus accumbens, the prelimbic cortex either motivates us to stop from acting or pushes us to act on a certain feeling or desire, said Kokane.
The researchers found an increased activity in the neurons connecting the prelimbic cortex to the nucleus accumbens during periods of abstinence, which may help the nucleus accumbens to drive relapse.
Drug use may then continue uncontrolled, often despite negative social and psychological consequences.
Kokane and McGinty believe that restoring normal activity in the neurons of the prelimbic cortex may prevent cue-induced relapse, but more research is needed.
Their study found that blocking PKA in the prelimbic cortex, an enzyme found to be more active during abstinence, locally returned neuronal activity to normal levels.
“When we infused the PKA inhibitor into the prelimbic cortex during heroin abstinence, we saw a decrease in cue-induced relapse,” said Kokane.
By blocking PKA, the researchers have discovered one way to restore control to the prelimbic cortex during abstinence from opioids in a rodent model. Importantly, reestablishing control within the brain also led to better behavioral control because heroin seeking was lowered. (PTI)
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