you're now at: MAIN :: Neurotransmitters I :: Serotonin :: The 5-HT1 receptors: 5-HT1A
You can recall (hopefully!) what I said about receptors in the section about basic neurobiology. (You did read that section, right? I suggest doing so if you haven't already.) They're simply proteins stuck in the membrane ("wall" of the neuron cell), and their purpose is to be on the business end (generally) of having messages sent/inhibited/etc. by a neurotransmitter.
The 5-HT1 (serotonin-1) family of receptors consists of different receptor proteins that nonetheless share striking similarities. Which explains why they call this a "family". The most well-studied of the 5-HT1 receptors include 5-HT1A, 5-HT1B, 5-HT1D, and 5HT-1E.
You already know where most of these receptors sit, so I'll spare the drawing(s) for now.
The 5-HT1 receptor family is probably the most implicated in the treatment of depression. Well, at least agonism (activation) of it is. However, different 5-HT1 receptors (it's a family, y'know) do have different effects in the body. This particular page will talk about the 5-HT1A receptor.
Agonism of this receptor is known to cause relaxation and relief of anxiety... I came to this conclusion, as buspirone (US: BUSPAR) is a 5-HT1A agonist that serves this purpose.
Most importantly, again, it's also believed that the 5-HT1A receptor is greatly involved in the treatment of depression, as evidenced in the "forced swim" test performed in rats treated with test (i.e., not on the market, well yet at least) 5-HT1A agonists.
This test is where a test animal (normally a rat) is put into a pool of (relatively) deep water and subsequently forced (by nature, of course, most rats don't want to drown!) to "tread water" (that's the nearest human equivalent I can think of). After some period of time, the animal, exhausted, will give up (and end up generally floating in the water). The animal is then re-exposed to the same situation the next day. Knowing that the previous day's situation was relatively hopeless, rats will give up treading water sooner the second time around than they did during the initial test.
This test is used as a huge benchmark to see if an antidepressant works. For an antidepressant to be considered successful in this test, an antidepressant-treated rat will have to be able to tread water for a longer period of time the second time around. Longer compared to a rat not treated with antidepressants, that is. Usually, even an antidepressant-treated rat won't tread water for longer than it did the first time it was exposed to the forced swim situation.
Of course, animal rights advocates do have their issues with this test, but trust me, it's one of the less cruel ones. At least they normally pull the rat out before it drowns (if the rat doesn't float by itself when it stops treading water).
Also, researchers have found that the 5-HT1A receptor is different in individuals with Borderline Personality Disorder (BPD; a personality disorder with features such as severe, rapid mood swings, very frequent suicidal ideation and actual completed suicide, and the inability to think about things as both good and bad at the same time, an issue known as "splitting").
How is the 5-HT1A receptor different in individuals with BPD (at least according to this study)? Remember that I said that our DNA, the genetic code, directs our bodies to assemble amino acids into useful bodily proteins (like receptors). Mutations (difference/s from what we consider "normal") in a gene can lead to the protein it "encodes" for acting differently. (Remember that our DNA instructs our bodies on how to produce useful protein molecules, such as receptors.) In this case, variations in the genetic code for the 5-HT1A receptor exist between people with and without BPD. The variation, of course, would most likely change how strongly serotonin can bind to this receptor and exert its effects.
What might be the most important thing, though, is that the 5-HT1A receptor isn't just for sending signals. It also can act as an "autoreceptor" in our brains.
WTF IS AN AUTORECEPTOR?
An autoreceptor is any receptor that controls the amount of a neurotransmitter in the associated synapse(s) by binding that exact same neurotransmitter. It's basically an overflow protection unit. Many types of receptors (such as our 5-HT1A here) have both autoreceptor and "postsynaptic" (message-sending) forms, generally in the same vicinity and likely the same nerve cell.
It has been shown that rats given flibanserin (a test 5-HT1A agonist and potential human antidepressant) will in the short-term show lower "available" (synaptic) serotonin levels in their brains (we assume that the serotonin went away through the reuptake pump!). This suggests that the 5-HT1A receptor is acting like a sentry, warning the synapse that there's too much serotonin in the brain. Sounds sad, right? But have no fear: The study also showed that if the 5-HT1A receptor keeps getting agonized all the time, it eventually (I have no idea what "eventually" means, these damn researchers just keep saying it) becomes de-sensitized, meaning that it does not act as much as it should. This in turn leads to relatively increased serotonin in the synapse, perhaps giving a reason for the almost ironic antidepressant effects seen in flibanserin and other 5-HT1A agonists.
Back to the short-term effects of activating the 5-HT1A receptor... this research also saw that in the short-term, more dopamine and norepinephrine (both associated with antidepressant effects) were available in the synapses when the test animals were treated with flibanserin.
Got all that? I know I barely did!
Another interesting tidbit is the fact that the blood pressure drug pindolol (US: VISKEN), which happens to act as a 5-HT1A antagonist in the brain, can make antidepressants work much faster and more effectively when taken together with them. (Well, at least according to a few studies, it can.)
How does pindolol work its magic? Remember from above that if you agonize the 5-HT1A autoreceptor for long periods of time, they just stop doing their job, leaving more serotonin in the synapse to transmit happy messages. The logic: Why not just directly block the 5-HT1A autoreceptor instead and not have to wait for it to go away by itself?
The above really is the theory on how pindolol can work its magic when given with other antidepressants, and gives us a little more insight on the 5-HT1A receptor.
