Summary: Oxytocin reduces drug seeking behavior in rats, a new study reports.
Many people have suggested that addiction hijacks the body’s natural drives in the service of compulsive drug use. A new study now suggests that hijacking another natural system in the brain may help overcome drug addiction. Published in Biological Psychiatry, the study shows that administration of oxytocin — a naturally occurring molecule well known for its role in social bonding and childbirth — reduces drug-seeking behavior in methamphetamine-addicted rats.
“There are virtually no pharmacotherapeutics for methamphetamine addiction, a chronically relapsing disease that destroys many lives,” said first author Dr. Brittney Cox, now at the University of California Irvine. “Our results are important because they support development of novel, oxytocin-based therapeutics for methamphetamine abuse in humans.”
To show this, Cox and colleagues developed a new method to assess addiction-like behaviors with meth, which could not be studied with previous techniques because of the drug’s long-acting effects. The researchers allowed rats to self-administer meth using a paradigm designed to examine individual differences in the rats’ drug-taking behavior, then tested the effects of oxytocin on their motivation to acquire the drug.
Although oxytocin administered to rats had no effect on the amount of methamphetamine they wanted when it required minimal effort, it strongly decreased the amount of effort rats were willing to exert to obtain the drug they desired, and it decreased relapse to methamphetamine seeking in both males and females.
“Intriguingly, these effects were strongest in animals with the greatest motivation to seek methamphetamine, indicating that oxytocin has potential as a treatment for addiction,” said Cox.
The study also pinpoints the brain region where the oxytocin has its effect. When Cox and colleagues infused oxytocin specifically into the nucleus accumbens, a small brain region implicated in drug addiction, they found that it had the same effects as when they administered it systemically. Infusion of an oxytocin blocker to the brain region blocked the systemic effects of oxytocin, driving home the necessary role of the nucleus accumbens for oxytocin’s effects.
“It will be interesting to learn whether oxytocin has a direct effect on the rewarding effects of methamphetamine or whether these effects are modulated by this hormone’s effects on natural rewards, particularly social activity,” said Dr. John Krystal, Editor of Biological Psychiatry, referring to the mechanism behind the effects that remains to be determined.
The researchers also found that using their new method, measures of motivation accurately predicted relapse behavior, which was not predicted by drug-taking itself when low effort was required. The technique used to assess addiction-like behavior in rats can also be used in humans, so if similar results are found in addicted people, the researchers hope the technique may help identify people most susceptible to addiction and be useful for predicting the efficacy of oxytocin treatment.
Source: Rhiannon Bugno – Elsevier
Image Source: NeuroscienceNews.com image is for illustrative purposes only.
Original Research: Abstract for “Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand” by Brittney M. Cox, Brandon S. Bentzley, Helaina Regen-Tuero, Ronald E. See, Carmela M. Reichel, and Gary Aston-Jones in Biological Psychiatry. Published online April 6 2017 doi:10.1016/j.biopsych.2016.11.011
Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand
Evidence indicates that oxytocin, an endogenous peptide well known for its role in social behaviors, childbirth, and lactation, is a promising addiction pharmacotherapy. We employed a within-session behavioral-economic (BE) procedure in rats to examine oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm was modeled after BE procedures used to assess motivation for drugs in humans with addiction. The same BE variables assessed across species have been shown to predict later relapse behavior. Thus, the translational potential of preclinical BE studies is particularly strong.
We tested the effects of systemic and microinfused oxytocin on demand for self-administered intravenous meth and reinstatement of extinguished meth seeking in male and female rats using a BE paradigm. Correlations between meth demand and meth seeking were assessed.
Female rats showed greater demand (i.e., motivation) for meth compared with male rats. In both male and female rats, meth demand predicted reinstatement of meth seeking, and systemic oxytocin decreased demand for meth and attenuated reinstatement to meth seeking. Oxytocin was most effective at decreasing meth demand and seeking in rats with the strongest motivation for drug. Finally, these effects of systemic oxytocin were mediated by actions in the nucleus accumbens.
Oxytocin decreases meth demand and seeking in both sexes, and these effects depend on oxytocin signaling in the nucleus accumbens. Overall, these data indicate that development of oxytocin-based therapies may be a promising treatment approach for meth addiction in humans.
“Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand” by Brittney M. Cox, Brandon S. Bentzley, Helaina Regen-Tuero, Ronald E. See, Carmela M. Reichel, and Gary Aston-Jones in Biological Psychiatry. Published online April 6 2017 doi:10.1016/j.biopsych.2016.11.011