By Dr. Priyom Bose, Ph.D. Mar 8 2024 Reviewed by Danielle Ellis, B.Sc.
A recent Brain and Behavior study investigated the antidepressant effect of dulaglutide and the mechanism that underlies this effect. Study: Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress. Image Credit: luchschenF/Shutterstock.com Background
Depression is a chronic mood disorder that is associated with low mood, insomnia, weight loss, a state of unhappiness, aversion to activity, fatigue, and low self-esteem. According to the World Health Organization, depression has become one of the major health burdens across the world.
This mental health condition is commonly treated with an antidepressant that takes around a month to alleviate the symptoms. However, several side effects are associated with the use of antidepressant drugs and could be toxic at high doses.
A combination of psychological, genetic, and neurological factors contributes to the manifestations of depression. Even though the exact etiology of this mental health issue is not fully understood, research has shown chronic stress to be an inducer of depression.
The hippocampus is a region of the brain that is associated with depression and modifies functionally and morphologically in response to stress. Animal model studies have shown that a decrease in neuronal and glial size, reduction in synaptic markers, loss of dendrites, and increase in apoptosis in the hippocampus leads to depression.
Many studies have uncovered the metabolic aspects of depression. For instance, diabetes and obesity are two common metabolic disorders that increase the risk of depression. Considering its high prevalence, novel therapies with high efficacy and fewer side effects are required to combat depression. The chronic mild stress (CMS) model has been recognized as a reliable rodent model to study depression.
Glucagon-like peptide-1 (GLP-1) and its receptor agonists are involved with anti-inflammatory effects and neuroprotective activities and can improve mental disorders, particularly depression and cognition. GLP-1 is a peptide hormone that stimulates the secretion of insulin and restricts the synthesis of glucagon in the pancreas in a glucose-dependent manner. Liraglutide is a GLP-1 analog that exhibited a positive effect in reducing anxiety and depression symptoms.
Dulaglutide is a novel long-acting GLP-1 receptor agonist that improves cognitive dysfunction and neuronal damage in rats with vascular dementia. Although many studies highlighted the efficacy of dulaglutide in preventing depression-like behavior triggered by chronic social defeat stress (CSDS), the underlying mechanism of this effect is not clearly understood. About the study
The current study used a metabolomics strategy to evaluate the effect of dulaglutide in a CMS model. Furthermore, the underlying mechanism of this effect was also assessed. Adult male ICR mice, which is a strain of albino mice, were selected for this study. All test mice were around seven weeks old.
After one week of acclimatization, 60 mice were randomly assigned in four groups, namely, control (CON), the CMS and Vehicle group (CMS+Veh), the CMS and 0.3 mg/kg dulaglutide group (Low Dula), and the CMS and 0.6 mg/kg dulaglutide group (High Dula). Except for the CON group, all other groups were exposed to stressors. Related StoriesSugar tax shows sweet results in cutting obesity and diabetes ratesAI-based model enhances efficiency of Type II diabetes prevention effortsStudy reveals mechanisms behind antidepressant effects of diabetes drug
To establish the CMS model of depression, selected mice were exposed to two or three different stressors for 28 days continuously. For stress induction, mice were deprived of water and food for 12 hours, kept in wet bedding for 24 hours, kept in a tilted cage for 24 hours, pintail for 1 minute, and cold water treatment for five minutes. The body weight of each test mouse was measured weekly, and behavioral tests, such as the tail suspension test (TST), open field test (OFT), and forced swimming test (FST), were performed. Study findings
The mice subjected to CMS for four weeks exhibited depressive- and anxiety-like symptoms. An LC-MS/MS metabolomics study was performed to understand the potential pathophysiological mechanisms and investigate the efficacy of drugs to alleviate depression-like symptoms.
A distinct difference between the CON group, CMS+Veh group, and High Dula group was observed in accordance with the metabolic disorders induced by chronic stress, which was altered through dulaglutide treatment. Many potential biomarkers were identified that are associated with purine metabolism, arginine and proline metabolism, glycerophospholipid metabolism, glutamate metabolism, sphingolipid metabolism, and bile secretion.
Lipid metabolism pathways could be potential targets through which dulaglutide alleviates depression. Lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), phosphatidylinositol (PI), sphingolipids, and phosphatidylcholine (PC), are involved with the therapeutic effect of dulaglutide in alleviating depression. Consistent with previous studies findings, this study highlighted the association between lipid metabolism and the antidepressant effect of dulaglutide.
The current study indicated the downregulation of N-acetyl-L-aspartic acid (NAA) in the CMS model group. NAA, which is one of the most important metabolites of the vertebrate nervous system, was found in decreased levels in rats with chronic, unpredictable, mild stress. However, the current study indicated that dulaglutide therapy increased the levels of NAA through its upregulation in the hippocampus.
In the CMS model group, an upregulation in L-glutamic acid and L-arginine was observed. Dulaglutide treatment caused a decrease in arginine and proline, thereby indirectly exhibiting a neuroprotective effect. Conclusions
The current study highlighted the antidepressant effects of dulaglutide using the CMS depression model. Notably, the potential metabolisms that underlie the antidepressant effect of dulaglutide have been elucidated in this study. Journal reference: Jin, M., Zhang, S., Huang, B., Li, L., Liang, H., Ni, A., Han, L., Liang, P., Liu, J., Shi, H. and Lv, P. (2024) Brain and Behavior, 14(3). doi: 10.1002/brb3.3448. https://onlinelibrary.wiley.com/doi/10.1002/brb3.3448?utm_medium=email
The 2025 Can-Am Origin electric motorcycle is the pinnacle of fun, just as long as your good time can fit into 69 miles of riding between charges. What it lacks in long-distance range, it makes up for in versatility, rugged style, and instant torque that’s ready for the road and trail. Each twist of the throttle delivers immediate electric propulsion. Its futuristic design and stealthy motor hum make the Origin a dual-sport machine pulled from tomorrow that wonderfully celebrates Can-Am’s two-wheeled heritage of decades past. I also spent some time on the road with the more approachable Can-Am Pulse, a standard street bike with a slight range advantage.
Can-Am style and comfort through technology
The Can-Am Origin is unlike any electric motorbike that has entered my garage. Its tall stance, 21-inch front and 18-inch rear wheels, and high ground clearance practically beg to be taken off your routine street routes. Can-Am simultaneously delivers an infotainment system on a dual-sport bike that, respectfully, makes much more expensive electric motorcycles look like tech dinosaurs in comparison.
The Origin’s dashboard has specs that every electric motorcycle company should copy. Equipping this system to an electric dual-sport feels like a total luxury. The Origin features a giant 10.25-inch color touchscreen with BRP Connect and a clean user interface that automatically switches between light and dark mode and adjusts brightness. In addition to a digital speedometer, you can quickly switch between ride modes, view battery status, check estimated range, and more.
Ride modes include Normal, Sport, Rain, Eco, two different Off-Road modes. You can toggle traction control and fine-tune front and rear regenerative braking independently, each with Off, Mid, and Max settings. Controls are accessible via the touchscreen when parked or through handlebar-mounted thumb controls while riding.
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The UI adapts to show either large gauges or a split between speedometer and infotainment applets. Bluetooth connects the bike and your phone, and Can-Am has included built-in wifi for over-the-air software updates. These are the kinds of features you’d expect on a premium electric motorcycle in 2025, but they’re not guaranteed.
For iPhone users, there’s Apple CarPlay integration. Two caveats: first, the system uses USB-A instead of USB-C, so newer iPhones will require an adapter or a USB-A to USB-C cable that supports data, not just charging. Second, it only supports wired CarPlay, not wireless, despite the bike having both wifi and Bluetooth radios onboard.
Those two complaints aside, the CarPlay integration is next-level. The touchscreen is responsive when parked, and everything remains fully controllable through the handlebar controls while riding. Access to apps like Maps, Music, Messages, and Phone while on the move is a real convenience. There are also motorcycle- and EV-specific apps with CarPlay are right at home on the Can-Am system.
There are no built-in speakers, so Can-Am relies on Bluetooth audio outputs. The setup is clever, supporting two output channels: one for the rider and one for the passenger helmet comms systems. I experimented by tossing a Bluetooth speaker onto the handlebars and was surprised to find it worked well in sub 50 mph environments as an open-air audio solution.
My only real hardware gripe on a bike that otherwise outshines much of its competition is the lack of self-canceling turn signals. Not every bike has them, but every bike that lacks them is missing out. There’s nothing less cool than riding around with your blinker still flashing. Fortunately, the dash clearly displays active signals. Still, I initially thought the right indicator light on the dash wasn’t working until I realized a single cable runs directly in front of it from my seated position. It’s a small, oddly specific problem that may be specific to my loaner bike, but I can’t quite position the cable differently.
Overall, I give the look and tech a 9.75 out of 10 for delivering both style and features that I actually want and use.
How the Origin feels to ride
At 5’10” with a 30-inch inseam, I find the Origin’s seat height tall yet correct for a dual-sport bike. Throwing a leg over feels a bit like saddling up on a horse, and once I’m on, it’s immediately comfortable. I can straddle the bike confidently, with my left foot planted on the ground and the other hovering around the rear brake. Any taller, and it might feel like a stretch; any shorter, and the ride position wouldn’t feel as commanding. The elevated stance provides a clear, confident view of the road or trail ahead, and the headlight system works adequately. It sets the Origin apart from the lower, more compact feel of traditional street bikes.
With this bike, Can-Am delivers an awesome mix of rugged reality and futuristic aesthetic. The Origin’s angular black-and-white bodywork and tall riding position regularly invokes the feeling of a stormtrooper hovering through the moon forest of Endor on a speeder bike. That particular vibe is especially strong at speed, where the elevated stance and electric torque make it feel like you’re gliding just above the terrain. At lower speeds, the illusion shifts. The stealthy motor hum fades behind the subtle roll of tires on pavement, creating a sensation much like quietly cruising up on a skateboard. It’s stealthy, smooth, and serene.
In terms of performance, the Origin tops out at 79 mph for me, providing plenty of speed for highway rides. Can-Am rates the 0-60 mph acceleration at 4.3 seconds, but frankly this bike feels like it might toss you overboard if you push it that quickly. Can-Am estimates range of up to 90 city miles and 71 mixed environment miles. On one test ride, I ran the battery from 100 percent to 1 percent over the course of 2.3 hours, covering 58.7 miles at an average speed of 24 mph, according to the bike stats.
According to my stats, it was many more hours of fun in the sun with a break for lunch at the park by the water in between riding sessions. That ride was done entirely in Sport mode with regenerative braking turned off, and it returned an average energy consumption of 9 miles per kilowatt-hour. It’s a solid showing for an electric dual-sport, especially considering the aggressive mode and lack of regen for the most reactive and relaxed ride.
Sometimes I love the feel of regenerative braking on electric cars and motorcycles. It can add to the feeling of responsiveness. I found regen on this bike to feel a bit more tight and underpowered for my liking, but it’s there as an option for extending range. With regen turned off entirely, the Origin felt significantly more loose and natural to ride. On the Origin I consistently opted to leave both front and rear regen off. We’ll see how the Pulse feels when I test that model next.
I must have logged over 500 miles across four weeks with the Origin. The lasting impression is that when you gain muscle memory for how the bike responds to throttle spin and body movement, riding the Can-Am Origin feels like playing an amplified electric guitar. Every incremental finger and palm positioning has a result, and when you find your rhythm, suddenly you’re creating music.
The other piece of the Can-Am Origin experience that I didn’t anticipate is the conversational aspect. Electric vehicles are still novel to many, and electric motorcycles are an absolute enigma to most. “Can it get wet?” is still the classic question that many ask. But from day one to day 28 of test riding the Can-Am Origin, it was the brand itself that got people asking me about the bike.
My takeaway is that people have a real affinity for the Can-Am brand as well as a nostalgia for the days of two-wheeled Can-Am motorbikes. When they learn that Can-Am is back on two wheels in the form of a bad-ass looking electric dual-sport motorcycle, people react like they just met a the much younger version of a celebrity in their home town. It’s a fun thing to experience.
Can-Am has earned its place as an electric motorcycle brand to consider
The Can-Am Origin is an incredibly thoughtful and fun take on what an electric dual-sport can be. It pairs rugged styling with a high-tech, feature-rich interface, offers plenty of real-world performance, and never stops turning heads while doing it without trying. From its futuristic design and surprisingly refined touchscreen to the tall, confident riding position and intuitive handling, the Origin is a complete package, so long as your expectations around electric motorcycle range are in check.
Priced starting at $14,999, the Origin slots in competitively against other premium electric motorcycles, though it leans more toward adventure and off-road versatility than urban street performance. It doesn’t quite reach the power or fast-charging capability of more premium priced machines, yet it undercuts in price and adds very useful touches like Apple CarPlay, OTA updates, and dual regen tuning.
If money were no object, I’d gladly keep one in the garage. It’s just flat-out fun to ride. From quick errands and joyrides to weekend backroad escapes, the Origin is a thrill machine that leaves you smiling between rides. Can-Am has a huge selection of first-party accessories to customize your bike as well. This configuration above makes me drool.
Range will be the limiter on machines like this for a while, and while around 70 miles between charges is enough for plenty of use cases, it still has to be a part of the conversation when talking recommendations. But here’s the thing: despite that limitation, electric motorcycles are a ton of fun right now. And if you’ve got either a high pain tolerance for early adoption or healthy access to good charging infrastructure, you can absolutely push them further.
The Origin is compatible with both Level 1 (standard wall outlet) and Level 2 (240V) charging, but not Level 3 DC fast charging. Can-Am rates Level 2 charging at 0 to 80% in 1.5 hours and 0 to 100% in 3.5 hours. In practice, that translates to plugging in and waiting a few hours between fun sessions. For some riders, that’s no big deal, especially if spending time at your destination is part of the trip.
I certainly don’t live along the great electric freeway of California, but my coastal stretch of highway in South Mississippi is populated with electric charging stops.
In my testing, I used the Can-Am Origin for a roundtrip airport commute from home in Ocean Springs, MS to Gulfport, MS, and back. The airport was outside of the travel-there-and-back-without-charging range, but free charging infrastructure at the airport parking garage made it no problem. I rode there, parked, charged during my trip, and returned from the other side of the country to a full battery. So yes, it’s capable of handling local duties. But if long range is central to your riding lifestyle, it’s something to plan around. I think lower speeds and paid charging solutions along the way would allow me to reach New Orleans and return home, but I haven’t set out on that path with this bike.
The Origin isn’t perfect, but it’s arguably best in its category, well-executed, and just damn cool to experience. Can-Am absolutely executed on creating a great electric motorcycle experience despite not being solely focused on EVs or two-wheeled machines.
Can-Am Pulse experience
After 600+ miles on the Can-Am Origin, I had the chance to put some miles on a 2025 Can-Am Pulse electric motorcycle. My key takeaways? Both are excellent electric motorcycles with equally great CarPlay integration. The Pulse is more approachable with a low riding position and slightly more range. The larger storage capacity is also appreciated compared to the somewhat tight space on the Origin.
Pulse ’73 edition with two-up configuration
If I were choosing which to purchase without extensive riding experience, the Can-Am Pulse is absolutely the bike I would gravitate toward. It’s just a great standard street bike with awesome technology at a competitive price.
Above is a look at the redesigned CarPlay experience coming in September 2025 to iPhone in iOS 26, as seen on the Can-Am Pulse display. The new design flexibility makes CarPlay look more at home next to Can-Am’s UI that always appears on a third of the display. Since Can-Am supports CarPlay, the infotainment system will receive free upgrades as Apple enhances the iPhone-powered feature.
Can-Am also supports free over-the-air software updates to the bike itself. Updates are downloaded over wifi and installed using the built-in system on the bike. No visits to the dealership or firmware updates over USB drives required.
Find more about Can-Am Origin and Pulse electric motorcycles here.
Electrek’s Take
I still think the Can-Am Pulse is the easier recommendation for most people, and you can kit it out as much as the Origin. Yet after around a month with each bike, I can’t help but think more about the Pulse. Can-Am really built a fun machine with that bike, especially with its commanding riding position and rugged style.
I would love to see a version with Level 3 charging speeds and greater range to expand the road trip potential, but both machines are super if your commute or leisure route works with the specs.
For now, Can-Am has delivered more than any other electric motorcycle maker when it comes to a giant display with CarPlay integration, attention-grabbing style, and options for two different riding preferences.
There’s something about the joy of playing around with Tonka trucks in a sandbox that men really never grow out of. Sure, we grow up, get real jobs, and most of us never take the toys back out of the dusty, long-forgotten box. But the desire is still there. And if you gave just about any former boy and reluctant adult the option, I’d be dollars to donuts they’d gladly play around with the life-sized version of their childhood construction toys in a heartbeat.
If that sounds like fun, then I’ve got good news for you. I just found the coolest grown-up toy construction vehicle and it’s unlike anything you’ve seen before. I’d argue that it slots in nicely as a perfect example of some of the coolest and weirdest things you can find from China’s endless supply of innovative EVs. So, for your viewing pleasure, I submit this week’s Awesomely Weird Alibaba Electric Vehicle of the Week: the Octo-dumper!
I really don’t know how to describe this vehicle. I’ve been at a loss for words before in this column, but at least there’s usually a general class of vehicle that these things fit into.
In this case, I’m hesitant to call it a dump truck – partly because it appears to be all dump and no truck.
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It’s remote-controlled, so you could call it an RC vehicle, but the fact that I’ve seen cars smaller than this rig makes me hesitant to lump it in with the remote-controlled toys.
Then there’s the 8×8 setup here. The last time I saw an eight-wheeled vehicle like this was, ironically, it was a mobile crane that was unloading one of my containers full of fun Alibaba construction equipment. Wow, I didn’t expect to come full circle there so quickly.
But despite being unable to quite classify this dumper, I still love everything about it, and I kind of want one.
Measuring around six feet long (197 cm), it seems capable of carrying a fairly large load. They rate it for 2,200 lb (1,000 kg) of cargo, and it looks every bit ready for it.
The top speed of 9 mph (15 km/h) might not hold up when fully laden, but this isn’t exactly a vehicle built for speed. Or comfort, for that matter. It’s built for by-god gettin’ stuff done! And with a claimed 5.4 kWh of battery capacity, it’s going to be quietly hauling your junk around for a good long time before it needs a recharge.
The cargo bed appears to have the classic pickup truck tailgate in the rear, though it also adds a pair of side gates like an old Corvair 95 Rampside pickup, except that the side gates run the full length. Finally, the front also has a tailgate–err, frontgate? Basically, it’s gates all around to turn this thing into a rolling flatbed capable of carrying just about any oversized junk you can think of!
Just don’t start tipping it up while you’ve got all those gates down or you might lose your load. That’s right, don’t forget that this is also a dumper! Not just a transporter around a job site, you can unload your dirt, mulch, gravel, friends, or whatever you carry in here with the push of a button.
Now I’m not exactly sure what I’d do with one of these if I owned one, but I’m sure I could find plenty of uses. You never realize what you can do with an octo-dumper until you own one, and then it’s suddenly like, “How did I ever manage without this thing!?”
Now it will set you back more than a Tonka truck. But I’d argue that the sticker price of $2,482 is a small price to pay in order to have the coolest vehicle in the neighborhood! Just try not to think yet about the thousands and thousands of dollars in fees, import charges, shipping, and other expenses of actually receiving one of these in the West. Instead, think of the fun hayrides you could give the neighborhood kids, at least assuming their parents signed the extensive liability waiver that this thing would probably require.
Speaking of liability though, before any of you get the bright idea to try one of these, please be warned that I’m telling you that’s a bad idea. As I always try to remind my readers during these fun tongue-in-cheek Alibaba articles: don’t actually try to buy one of these things. Seriously. These wild-looking Chinese EVs may be fun to look at, but this is just a lighthearted weekend column where I dig through Alibaba’s bizarre and fascinating collection of electric vehicles. While I’ve had a few successful (and fun) purchases from the site, I’ve also been burned more than once – so it’s definitely not for the faint of heart or anyone on a tight budget.
That’s not to say some brave (or stubborn) readers haven’t taken the plunge anyway, ignoring my caution and venturing into the unknown. But please don’t be the one who gambles and ends up with empty hands and a lighter wallet. Consider this your official heads-up – I’ve warned you!
For now, let’s enjoy how awesome it is that something like this octo-dumper exists, and leave it at that. Until next time, and until the next weird Alibaba EV, this is Micah signing off.
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