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Beatrice Bowlby
New research pinpoints neurons involved in maintaining motivation in rats, potentially paving the way towards new treatments for ADHD, depression and addiction.
While studying reward-seeking behavior in rats, researchers from Nagoya University (Japan) discovered the essential role of orexin neurons in the brain mechanism underpinning motivation. The findings have implications for the treatment of conditions characterized by motivational deficits, including attention-deficit/hyperactivity disorder (ADHD), depression and addiction.
Orexin neurons are specialized nerve cells found in the hypothalamus that regulate several essential physiological functions such as energy homeostasis, wakefulness, cognition and mood. Recent research has suggested that they also have a part to play in motivated behaviors, although the exact reasons for this remain uncertain.
Hoping to change that, scientists used rats to investigate how orexin neuron activity impacts the animals’ drive to obtain food rewards. Thus far, technical challenges have stymied scientists’ ability to target specific neurons in rats in a temporally controlled manner; hence, previous research has largely relied on mice, which offer a less sophisticated model of behavior.
To overcome these technical hurdles, the team developed transgenic rats, whereby Cre-recombinase is expressed exclusively in orexin neurons, allowing them to precisely target these nerve cells. They used chemogenetics to activate orexin neurons, then conducted a progressive ratio test, gradually increasing the number of touches required to earn a food reward. To gauge the rodent’s motivation intensity, they measured how long it took for the rats to give up their search for a snack, called the breakpoint.
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In doing so, they demonstrated that when orexin neurons were activated, breakpoints were higher, showing increased motivation for a reward. On the other hand, when orexin neurons were selectively degenerated, breakpoints were lower and motivation reduced.
Moreover, fiber photometry experiments revealed that during motivated behavior, orexin neuron activity changed dynamically, increasing before and decreasing after the reward was received. When the reward was not obtained, this elevated activity was sustained. Interestingly, orexin neuron activity was stronger the more effort the rats made.
When the researchers used optogenetics, as well as an orexin 1-receptor antagonist, to inhibit orexin neuron activation while the rats were expecting a reward, reward-seeking behavior lessened. However, there was no increase in motivated behavior when an agonist was used to excite orexin neurons at this stage.
This suggests that, although orexin neurons are required for sustaining motivation, artificially overstimulating them is not sufficient on its own to boost it.
Summarizing these findings, study lead Hiroyuki Mizoguchi concluded: “Our study demonstrated significant changes in orexin neuron activity depending on expected rewards and the effort required, suggesting a potential mechanism for translating expectations into sustained action.”
It is Mizoguchi and colleagues’ hope that by furthering our understanding of the orexinergic mechanisms behind motivation, their work could contribute toward novel treatments for disorders in which it is diminished.
The post The neuroscience of motivation: how does the brain sustain its drive? appeared first on BioTechniques.
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