Fall 2015

Like Minds

Animal behavior research holds promise for better detection and treatment of compulsive disorders in people 

By Genevieve Rajewski

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Illustration: Martin O'Neill

In 2011, science threw a curve ball at Nicholas Dodman, head of the Behavior Clinic at the veterinary school at Tufts, and his colleague Alice Moon-Fanelli. The researchers were looking at bull terriers in hopes of finding the gene responsible for a debilitating behavior common in the breed. Up to 85 percent of any litter will compulsively chase their tails, sometimes to the point of savaging themselves or anyone who tries to interrupt them.

A statistical analysis of data, including sex, medical history and other behaviors found in 145 affected bull terriers and 188 “control” pets revealed some surprises. The vast majority of affected dogs were males, and many had other strange behaviors or physical conditions that accompanied the tail chasing, such as explosive aggression, partial seizures, phobias, skin conditions, gastrointestinal issues, object fixation and a tendency to shy away from people and other dogs.

“How could we possibly explain this?” Dodman recalls, before he realized there were similarities between these canine behaviors and autism in people. “The primary behavioral expression of autism in humans is that a child is slow to develop speech and other social behaviors,” he says. “But if you weren’t able to factor speech into the equation, you may still observe repetitive behaviors like spinning, rocking or flapping hands, temper outbursts and sometimes seizures. Affected bull terriers show many of these behaviors.”

Indeed, when Dodman, Moon-Fanelli and researchers from the Sackler School of Graduate Biomedical Sciences looked for biological similarities between the tail-chasing bull terriers and children diagnosed with autism, they found significantly elevated levels of two biomarkers in the children and the dogs. Their findings were published in Translational Psychiatry in October 2014.

Quelling the Skeptics

The notion that behavioral disorders in people and animals might share some commonalities has long met with skepticism in scientific circles. But Tufts researchers have helped move that concept from anthropomorphism to evidence-based science that has led to new treatments for people and pets—including a new patent on a drug to treat obsessive-compulsive disorder in humans.

Dodman never intended to specialize in the animal mind. However, not long after he arrived at Tufts’ veterinary school in 1981, he received a call from Louis Shuster, a pharmacologist at Tufts Medical School who was studying drug abuse.

“We could control the horse’s behavior by controlling its brain behavior. It was the eureka moment that changed all our lives.” —Nicholas Dodman

Shuster had read a scientific paper about racehorses becomingly increasingly sensitive to the stimulant effects of morphine with every dose, instead of more tolerant of the drug as is typical in people. He had observed the same bizarre phenomenon in rodents exposed to opioids and enlisted Dodman for a study that confirmed that exposure to morphine indeed led to similar behaviors in horses.

The morphine-induced equine behaviors—endlessly pacing the stall or digging at the ground—overlapped with what equestrians call “stall vices,” says Dodman. In animals, these abnormal, seemingly pointless and sometimes self-injurious behaviors are referred to as “stereotypies.” Because stereotypies are common in horses kept stabled most of the time, Dodman wondered if that might mean the horses were “self-medicating” to cope with the stress of confinement. “I thought the abnormal behavior could be due to nature’s own morphine: the endorphins.”

Shuster agreed, and they set out to determine if a medication that blocks the body from responding to opioids and endorphins could rein in stall vices.

Eureka Poker

They turned to Poker’s Queen Bee, a palomino mare that engaged in “cribbing,” a behavior in which horses clamp down on a stall door or fence, tense their neck muscles and repeatedly gulp air. Dodman and Shuster plotted the incidence of the mare’s cribbing before and after she was injected, first with control doses of saline and then with the opioid-blocking drug naloxone (the Narcan now used to treat heroin overdoses).

The opioid blocker worked. “We could control the horse’s behavior by controlling its brain behavior,” Dodman says. “We turned the infusion rate up, and the horse stopped cribbing. We turned it down, and it started cribbing again. It was the eureka moment that changed all our lives.”

Shuster shifted his research focus from the drugs of addiction to the behaviors of addiction. And Dodman found a new calling: treating animal behavior problems.

After working with horses through the 1980s, Dodman and Shuster started studying dogs with stereotypies, particularly those with lick granulomas, a condition in which pets create an open wound by licking their leg repetitively. Again the duo found that drugs that blocked the body from responding to opioids lessened the repetitive behavior.

In both animals and people, repetitive behaviors often stem from anxiety, and engaging in them appears to bring some relief, says Dodman. But the relief is fleeting, and the OCD loop is on an endless repeat. While treatment for people with OCD usually involves cognitive behavioral therapy, pets’ compulsive behavior is managed by changes to their environment that will reduce stress and a class of mood-stabilizing drugs that includes Prozac.

Dodman and Shuster, now a professor emeritus, have identified a new OCD drug designed to improve the lives of animal with compulsive behaviors. When they studied opioid-blocking drugs in mice, dogs and horses, they realized that those same drugs also blocked NMDA receptors, which help the body process glutamate, a neurotransmitter that’s important for cognition, memory and learning. When they tested drugs that block glutamate, such as dextromethorphan or memantine, on compulsive behaviors, mice stopped their self-scratching, and many of the dogs showed a significant reduction in their compulsive behaviors.

The two approached Michael Jenike, head of the Obsessive Compulsive Disorders Institute at McLean Hospital in Belmont, Massachusetts, who was convinced enough to try memantine on a few of his patients who did not respond to selective serotonin reuptake inhibitors (SSRIs). After the patients reported improvements in their symptoms, the three researchers conducted a study comparing 22 people with OCD receiving cognitive behavioral therapy with 22 OCD patients who also took memantine.

Only the memantine-takers saw significant decreases in their OCD symptoms, according to their study, published in the Journal of Clinical Psychopharmacology in 2013. Tufts patented memantine as a new treatment for OCD, and psychiatrists are now using it alongside SSRIs in people with better results.

Pets could play an important role in understanding which genes influence the brain and thus modify behavior in animals with compulsive tendencies.

Despite these outcomes, most scientists who study human psychiatric conditions, including Jenike, will not entertain the idea of too many similarities between a behavior disorder in humans, a species that has landed on the moon, and one in dogs, a species known to sneak snacks from unguarded litterboxes. “I have a hard time with the concept of a dog biting on his leg and calling it OCD,” Jenike told Science magazine in 2010. “With OCD, you need to know what’s going on in the head. It’s kind of a big leap for me.”

Nonetheless, pets—particularly purebred dogs and their very similar DNA blueprints—could play an important role in understanding which genes influence the brain and thus modify behavior in animals with compulsive tendencies. “It’s become very clear over the past decade that although we have amazing new genomic and genetic tools, it’s still very difficult to find disease genes [in humans] for many neuropsychiatric disorders, particularly those associated with behavioral differences such as what we observe in autism,” says Matthew Huentelman, an associate professor in the Neurogenomics Division of the Translational Genomics Research Institute in Arizona. “So while we aren’t stopping our work in human beings, working in purebred animals should dramatically simplify things for us on the genetics side.”

This story first appeared in the Summer 2015 issue of Cummings Veterinary Medicine magazine. The author can be reached at genevieve.rajewski@tufts.edu.

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