A new study has found that even brief use of the opioid oxycodone can lead to lasting behavioral impairments in rats. The team of researchers believes the drug may cause a “cognitive hangover,” leading to enduring changes in brain structure that impact behavioral flexibility and decision-making skills. The study also suggests that the amount of cognitive hangover provides insight into why some people are more likely to develop an addiction than others.
Published in the journal Learning and Memory, the team from the Icahn School of Medicine at Mount Sinai’s chief concern was behavioral flexibility, or the ability to select new responses when more unfamiliar circumstances occur. Where past studies have found that behavioral flexibility is impaired when exposed to prolonged dosages of cocaine and amphetamines, the effects of a typical dose of oxycodone have not been investigated as of yet.
Studies have shown that in people and rodents exposed to stimulants, repeated actions can become automated and resistant to change. This leads to changes in the prefrontal regions of the brain, resulting in a loss of flexibility in altering behavior (essentially what makes an addiction such a difficult habit to break).
“Oxycodone binds to opiate receptors that are distributed throughout brain systems involved in important learning and memory processes. Our data suggests that even relatively limited exposure to oxycodone can impair how these brain circuits are able to guide behavior. These impairments affect decision-making and could be one reason why people continue to use or abuse the drugs, long after they are medically necessary,” said Katharine M. Seip-Cammack, Ph.D., lead author of the study.
For the study, the researchers subjected rats to five days of oxycodone, dosed comparably to what is prescribed for post-surgical pain relief in humans. After using a series of learning and memory tasks (mazes, memory retention and motor habit tests), they discovered that days after the drug’s initial duration, the now sober rats responded in more maladaptive ways, suggesting that the more stubborn behavior is a result of impaired cognitive flexibility.
The authors also found their memory to be compromised when performing in habitual tasks, supporting the theory that striatal function plays a role in learning new behaviors. The striatum, located in the basal ganglia in the center of the brain, contain spidery cholinergic interneurons that respond to acetylcholine, a neurotransmitter that is believed to determine the way we view learning new habits.
However, not all of the rats exposed to oxycodone showed impairments; some learned the new mazes at the same rate as the control group that was exposed to a saline-solution. This suggests that they either had less neural plasticity to begin with, allowing less adverse effects on their neural structures, or simply had relatively more developed cognitive networks to begin with.
Breaking the addiction cycle
Oxycodone, as well as all illicit drugs, can alter the brain’s reward system, setting it on a course of addictive behavior. However, there are many techniques that can reverse the effects of substance dependency, such as brain mapping and neurofeedback, which uses displays of brain activity in real-time (most commonly electroencephalography (EEG) waves) to teach self-regulation of various brain functions.
If you would like more information about treatment options for substance abuse, feel free to contact our 24/7 helpline listed above.