Little Furry Addicts Help Us See How Our Brains Feed Addiction

A picture of a lab rat with an icon of a razor blade and cocaine overlaid.

In a lab at the University of Michigan dozens of rats scurried around their cages waiting for their next cocaine fix. But these weren’t your average drug addicts.

Their brains were outfitted with fiber-optic implants and their brain cells genetically modified to respond to certain light. When given the option between a dose of intravenous cocaine or cocaine plus a little extra brain stimulation, the rats overwhelmingly chose the combination – and their addiction worsened.

The scientists monitoring their actions are looking for specific clues as to how a particular part of the brain contributes to addiction. A better understanding of this connection will help develop new therapies.

Addiction is a disease characterized by an extreme, irrational desire for a specific rewarding stimuli. Several factors might contribute to the development of addiction – like health or social pressures – but the process is primarily biological. Repeat exposure to an addictive stimulus hijacks our body’s complex inner reward system and creates a destructive feedback loop that results in unusually intense and focused motivation. Understanding how our brain generates such extreme and specific desire is key to treating the disease but has been a challenge for neuroscientists.

Nestled deep inside the rat’s brains (and ours) sits the amygdala, two almond-shaped clumps of brain cells – or neurons – that play an important role in how decisions are made and addiction is formed.

Researchers think this small cluster of neurons might be particularly responsible for the intense urges that drive addiction. In humans, certain cues activate this region of the brain and generate desire to seek out the substance or activity associated with reward. The fiber optic implants surgically implanted in the rat’s amygdala provided a direct conduit to trigger parts of the amygdala, mimicking the neurological effects of a cue.

One group of rats in the study were given two options: poke a small porthole and receive a dose of cocaine directly into their bloodstream or poke a second porthole that provided the same cocaine but also sent a pulse of light through their implants, activating their genetically modified, light sensitive brain cells. By triggering those neurons the researchers learned to what extent this area of the brain enhances motivation for reward. Would that rats prefer one option over the other and if so, how strong would their preference be?

In all cases, the combination of cocaine and the pulse of light seemed to greatly magnify the intensity of the rat’s desire for that porthole, even though they were receiving the same amount of cocaine from both.

“What was most surprising about our results is that not only did the amygdala stimulation intensely bias the rats’ choice for a particular cocaine reward, it made them want that cocaine so much more than under normal situations,” says Dr. Shelley Warlow, the lead author on the project and postdoctoral scholar at the University of California San Diego.

The combination had an exponential effect on the rat’s desire and fit the familiar pattern of rapid increase in drug use from addiction. Overall, the rats were willing to work around eight times harder for the light pulse and cocaine fix than when only given the option for cocaine. A separate group of rats were tested using just the light pulse with no cocaine reward at all. They showed no preference, indicating that the firing of those neurons alone was not a motivation for reward.

Later on in the study additional tests explored whether inhibiting this area of the brain through various means had any effect on the cocaine light pairing. Microinjections of muscimol, a psychoactive substance derived from a mushroom, and baclofen, a central nervous system depressant, completely removed the intensifying effects of the light cue.

“I think our results can help inform future treatments that precisely target brain areas, such as deep brain stimulation,” says Warlow. Targeting specific cells in the amygdala could curb or possibly even eliminate the intense drug cravings and uncontrollable seeking that addicts experience; and lead to new paths of recovery.

Dr. Warlow and her team are now exploring whether these effects hold true with opioids as well.

Read the Full Paper

Warlow SM, Robinson MJF, Berridge KC. Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for CocaineJ Neurosci. 2017;37(35):8330-8348.