Researchers at the University of Michigan Analyze Spine Density in Addiction-Prone Rats with Neurolucida

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Drugs affect different people in different ways. Take cocaine for example. Not only does the drug have a stronger impact on the behavior of individuals with a particular genetic makeup, it also  initiates more profound changes in their brains.


Researchers at the University of Michigan are studying brain plasticity in cocaine-treated rats after a period of abstinence. They’re studying how abstinence from the drug affects different types of rats – those with an “addictive personality” versus their less addicted cousins.


To determine the effects of cocaine abstinence on these two groups, the researchers studied specially bred lines of rats. One group was highly sensitive to cocaine, while the other group didn’t respond as strongly to the drug. Known as “high-responder rats” (bHR) and “low-responder rats” (bLR), the two groups reacted differently to the drug treatment, with bHR rats acting more agitated during cocaine treatment, and their brains displaying more pronounced plastic changes after a period of abstinence.



Dendritic spines were quantified on terminal dendrites of medium spiny neurons (MSNs) in the nucleus accumbens core sub region of selectively-bred high- and low-responder rats following repeated cocaine treatment.

During the course of the study, both groups were given escalating doses of cocaine over nine days, during which time their behavior was tested. Twenty-eight days after ending the drug treatment, the rats were euthanized and their brains sectioned.


Using Neurolucida to analyze images of DiI-labeled medium spiny neurons in the nucleus accumbens core sub-region (AbcC) of rats, the scientists saw a decrease of 37 percent in total spine density in bHRs. They saw the most pronounced changes near the branch point of terminal dendrites, where branched spines were decreased by 91 percent, and the lowest effects in mushroom spines, which decreased by 23 percent. Mushroom spines also decreased in bLR rats, according to the paper, which will be published in Neuroscience.


“Relative to bLRs, bHR rats appear to be especially sensitive to both the behavioral and neurobiological effects of repeated cocaine treatment,” the authors say.


According to the paper, changes in dendritic spine density may be “mediated by dysregulation of dopamine-glutamate signaling,” and the authors speculate that differences in the way neurotransmitter systems are regulated in the two groups of rats may be the reason why their brains react differently to the drug treatment.


“These bHR-bLR differences are a consequence of the prolonged abstinence following cocaine exposure, a time period during which individual differences in the expression of genes associated with neuroplasticity are most robust,” they say.


M. Waselus, S.B. Flagel, J.P. Jedynak, H. Akil, T.E. Robinson, S.J. Watson Jr., Long- term effects of cocaine experience on neuroplasticity in the nucleus accumbens core of addiction-prone rats, Neuroscience (2013), doi: