How Scientists Are Increasing Antidepressant Effectiveness To Better Treat Depression. FPS #1

In this inaugural release of First-Person Science, Roger Hudson speaks with Thomas Lapointe about his recently published manuscript that explores the behavioural and brain mRNA effects of combined escitalopram (an SSRI; antidepressant) and adjunct aripiprazole (5-HT1a agonist) in rats, with a specific focus on the 5-HT1a receptor. This podcast also discusses how scientists are enhancing the therapeutic efficacy of antidepressants and some of the mechanisms involved.

“Effects of combined escitalopram and aripiprazole in rats: role of the 5-HT1a receptor”, published in Psychopharmacology [2019 Jul;236(7):2273-2281] / DOI:10.1007/s00213-019-05225-z.

Manuscript Abstract:
Pre-clinical and clinical studies have suggested that the antidepressant efficacy of escitalopram (ESC) can be augmented by co-administration of aripiprazole (ARI).

To establish if the effects of ESC + ARI can be altered by modulating the 5-HT1a receptor.

Sprague-Dawley male rats received ESC + ARI (10 and 2 mg/kg/day, respectively, via osmotic or by cumulative injections), as well as the 5-HT1a antagonist WAY-100635 (WAY; 0.01-1 mg/kg) and the 5-HT1a agonist 8-OH-DPAT (DPAT; 0.3-1 mg/kg) prior to testing in locomotion chambers and in the forced swim test (FST). Expression of the 5-HT1a receptor mRNA in the dorsal raphe nucleus, hippocampus, septum, and entorhinal cortex was also assessed.

WAY generally synergized, while DPAT antagonized, the effect of ESC + ARI on motor activity. All groups showed significantly lower 5-HT1a mRNA in the dorsal raphe nucleus. In the hippocampus, ESC + ARI and WAY + ESC + ARI groups displayed equivalent elevations of 5-HT1a mRNA, but this was not observed in groups that received DPAT + ESC + ARI. Finally, the addition of ARI to ESC augmented the effect that ESC alone had on reducing immobility in the FST. Importantly, WAY antagonized this effect, while DPAT had no consequences.

Taken together, these results in rats indicate that the 5-HT1a receptor is involved in the behavioral and brain region-specific mRNA effects of ESC + ARI.

KEYWORDS: 5-HT1a receptor; Antidepressant; Aripiprazole; Augmentation; Depression; Escitalopram; Forced swim; Psychomotor; SSRI; mRNA

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First-Person Science is the first and only Webcast dedicated to in-depth exploration of scientific research articles w/ first-hand perspectives & narratives from the authors themselves. We aim to increase promotion of neuroscience research articles and provide exposure for the scientists behind the work, as well as enhance public accessibility to publicly-funded, cutting-edge research.

Watch the full interview here:

Once an addict, always an addict: True for the brain? Origins of the addiction neuroscience wanting vs. liking dichotomy

In this clip we comment on the landmark neuroscience publication that began the ‘wanting/liking’ dichotomy that researchers are still using to investgate addiction-related processes to this day. Titled “The neural basis of drug craving: An incentive-sensitization theory of addiction”, Terry E. Robinson & Kent C. Berridge present insights on the psychology of addiction.

The theory addresses three fundamental questions.
1) why do addicts crave drugs?
2) why does drug craving persist even after long periods of abstinence?
3) Whether ‘wanting’ drugs (drug craving) is attributable to ‘liking’ drugs (to the subjective pleasurable effects of drugs)? Or possibly due to external components altogether.

The theory of addiction suggests:

  1. Addictive drugs enhance dopamine transmission in brain reward areas.
  2. A major psychological function of this neural system is to attribute ‘incentive salience’ to events associated with activation of the system (drug cues and stimuli).
  3. In some individuals the repeated use of addictive drugs produces adaptations in this system, rendering it increasingly and perhaps permanently, hypersensitive (‘sensitized’) to drugs and drug-associated stimuli. This is ultimately a learning & memory based effect.

open access articles:

Join us for NeuroBeer every Monday (8pm EDT) & NeuroDrugs every Wednesday (9pm EDT) on YouTube for the largest interactive live streaming journal club & contribute to the conversation! Stay tuned to stay up to date with the latest in neuroscience news.

How are dopamine vs opioids involved in wanting vs liking? Is only dopamine involved in motivation? Or opioids too? How does motivation impact drug addiction? How does dopamine affect addiction and wanting vs liking addictive drugs? Can the addicted brain go back to normal? If so, how long does it take for the addicted brain to go back to normal, or when brain dopamine receptor levels take to return to baseline following addiction? As the saying goes, once an addict, always an addict, but is this true for the brain? What are the four fs, and how does dopamine regulate them? And how does learning and memory come into play?

From NeuroDrugs live #2. Short clip: streamed live July 15, 2020. Full conversation:

2020 CAN Outreach and Advocacy Award winner

We are excited to announce that the First-Person Science team has won the 2020 CAN Outreach and Advocacy Award!

The award recognizes the important efforts of First-Person Science to “present information about neuroscience discoveries in a way that is accessible to the public, through interactive live stream conversations with researchers.”

Our team works incredibly hard to provide content across multiple mediums to help inform the public and engage with viewers. With over 30 YouTube videos, Twitch live streams twice a week, over a dozen podcast episodes and countless social media posts, we continue to work towards a more informed and scientifically literate society.

The First-Person Science team is so grateful to all of those that have supported us in our quest to make neuroscience accessible. This would not have been possible without YOU, the critical thinkers that seek informed perspectives on nuanced issues. So for that, we thank you.

We look forward to continuing the process of bringing you informed, accurate and knowledgable episodes.