Cocaine-seeking behaviors and sugar-seeking behaviors activate different ensembles of neurons in the rodent brain, according to new research published in Molecular Psychiatry. The findings suggest that it may be possible to selectively target drug reward seeking while leaving natural reward seeking intact.
“All rewards (drugs of abuse or natural rewards such as food or water) active brain regions within the reward pathway. However, drugs have shown to induce specific changes in the brain that are not usually seen with natural rewards (except in pathological contexts like eating disorders or some behavioral addictions),” said study author Ana Clara Bobadilla (@AnaclaraBob), an assistant professor at the University of Wyoming.
“We were interested in dissecting what network of cells, or neuronal ensembles, were specific to seeking drugs (cocaine in this paradigm) versus natural rewards (sugar).”
The researchers were particularly interested in the nucleus accumbens, a key reward processing region in the brain that has been implicated in addictive disorders. Using genetically modified mice, Bobadilla and her colleagues found that sucrose and cocaine ensembles recruited mostly dopamine D1 receptors. These results are in line with the general understanding in the field that activation of the D1 pathway promotes reward seeking, while D2 pathway activation can lead to aversion or reduced seeking.
But cocaine recruited an ensemble of neurons that was largely distinct from the neurons recruited by sucrose. Only about 30% of the cells activated during cocaine seeking were also activated during sucrose seeking.
“We established that in the nucleus accumbens, the neuronal ensembles (i.e. a sparse network of neurons activated simultaneously) are reward-specific, and sucrose and cocaine ensembles are mostly non-overlapping,” Bobadilla told PsyPost.
“In humans, drugs are rarely used in the vacuum. Most of us have complex lives including lots of sources of nondrug rewards, such as food, water, social interaction or sex. Like drugs, these rewards drive and influence our behavior constantly.”
“This study is important because establishing that cocaine recruits an ensemble of neurons largely distinct from neurons recruited into an ensemble coding for sucrose seeking poses the possibility to therapeutically target maladaptive drug seeking without affecting biologically adaptive reward seeking,” Bobadilla added.
But the study — like all research — includes some limitations.
“One caveat is that simultaneous activation of neurons during a behavior does not imply these neurons are necessary for the behavior. In other words, correlation does not equal causality. Moving forward, we are working to show causality by demonstrating that activation of these ensembles do induce seeking behavior for cocaine or sucrose,” Bobadilla explained.
She is now focused on the question of how cells are recruited in ensembles and hopes to address another question in addiction research: whether the network-specific mechanisms for cocaine underlie the seeking of all drug rewards.
“All drugs of abuse share high probability of relapse,” Bobadilla said. “However, each class of addictive drug displays different acute pharmacology and synaptic plasticity. We are now investigating if reward-specific properties of ensembles can explain these differences.”
The study, “Cocaine and sucrose rewards recruit different seeking ensembles in the nucleus accumbens core“, was authored by Ana-Clara Bobadilla, Eric Dereschewitz, Lucio Vaccaro, Jasper A. Heinsbroek, Michael D. Scofield, and Peter W. Kalivas.
