Adolescent Xanax exposure increases neurobiological sensitivity to opioids

A new study published in Scientific reports highlights the lasting effects of the drug alprazolam, commonly known as Xanax, when used during adolescence. Using male mice as subjects, researchers found that exposure to the drug at a young age could increase the animals’ sensitivity to opiates, such as morphine, even long after exposure to the drug had ended. This research highlights the potentially negative long-term consequences of using certain drugs during critical stages of development.

Benzodiazepines, including alprazolam, are frequently prescribed to treat anxiety, insomnia and other disorders, but carry risks such as dependence and dependence. Despite their known dangers, alprazolam remains heavily prescribed, often misused alongside other substances like opioids. This misuse is of particular concern among adolescents, who may not fully understand the risks involved.

Previous research has primarily focused on older adults, leaving a significant gap in understanding how these drugs affect younger people. Recognizing this gap, researchers set out to explore the specific impacts of alprazolam on adolescent development.

“In our lab, we study the effects of early exposure to psychotropic medications and stress on brain biochemistry and behavior,” said study author Astrid M. Cardona-Acosta of Texas A&M University. “We were particularly interested in the effects of benzodiazepines, particularly alprazolam (Xanax), due to their high prescription rates in the general population and their popularity among adolescents for recreational use. Xanax is popular all over the world.

The study used male mice in the adolescent developmental stage. They were kept under temperature-controlled conditions with a constant light-dark cycle (12 hours each), mimicking natural environmental conditions.

Alprazolam, the study drug, was administered at doses of 0.5 mg/kg and 1.0 mg/kg once daily for 14 consecutive days. These doses were chosen based on previous studies to reflect levels of recreational use that are likely to induce behavioral effects without causing overt toxicity or distress. A control group received a vehicle solution mimicking the administration procedure but without the active drug.

To assess the rewarding effects of opiates potentially modified by prior exposure to alprazolam, researchers used the conditioned place preference (CPP) paradigm. This method is widely used in behavioral neuroscience to measure preference for an environment associated with drug administration.

The results showed that mice pretreated with alprazolam developed a strong preference for environments associated with even subthreshold doses of morphine. This effect was evident not only in the short term, 24 hours after the last exposure to alprazolam, but also in the long term, one month after exposure.

“In a nutshell, the most surprising finding was that the increased sensitivity to relatively low doses of opiates (in this case, morphine) was still present a month after the last experience with Xanax,” Cardona said -Acosta at PsyPost.

At the biochemical level, researchers discovered changes in signaling pathways within two critical brain areas involved in reward processing: the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Specifically, there was notable dysregulation of the ERK signaling pathway, a key cellular mechanism involved in transmitting signals from the cell surface to DNA in the nucleus. This pathway is primarily responsible for regulating processes such as cell division, differentiation and survival.

Shortly after alprazolam treatment, there was a decrease in mRNA expression of ERK and its downstream targets within the VTA, while protein phosphorylation levels increased. These changes suggest a complex regulatory response that could increase the brain’s sensitivity to other drugs.

One month after alprazolam exposure, lasting alterations were still evident, indicating long-term neurobiological changes. The continued dysregulation of ERK-related signaling components suggests that the adolescent brain undergoes significant changes in response to alprazolam that persist into adulthood.

“The main takeaway from our published study is that drug use during sensitive developmental periods such as adolescence can have long-term negative consequences,” Cardona-Acosta explained. “In this case, increased sensitivity to opiates. Additionally, our study could raise awareness of the potential dangers of long-term use of certain medications during periods when the brain is still maturing.

Animal models play a vital role in biomedical research due to their biological and physiological similarities to humans. Many fundamental biological and behavioral processes are conserved across mammalian species, and the use of animal models allows researchers to control for environmental factors and genetic background, which is essential for reducing variability and increasing data reliability. But translating the findings from mice to humans still requires careful consideration and further validation.

Ultimately, researchers hope to better understand the neurobiological causes of drug addiction, which could pave the way for developing more effective treatment strategies. “Understanding the effects of drug use/exposure during adolescence on the developing brain can give us insight into how the brain will respond to other challenges (drugs, stress) once it matures ” Cardona-Acosta said.

The study entitled “Exposure to alprazolam during adolescence induces lasting dysregulation of sensitivity to morphine reward and second messenger signaling in the VTA-NAc pathway” was written by Astrid M. Cardona-Acosta, Omar K. Sial, Lyonna F. Parise, Tamara Gnecco, Giselle Enriquez Marti, and Carlos A. Bolaños-Guzmán.

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