It is a G protein-coupled receptor (GPCR), coupled to the Gi protein, and its activation in the brain mediates hyperpolarization and reduction of firing rate of the postsynaptic neuron.
[11][12] Vasodilation of the blood vessels in the skin via central 5-HT1A activation increases heat dissipation from the organism out into the environment, causing a decrease in body temperature.
Some of the atypical antipsychotics like lurasidone[25] and aripiprazole[26] are also partial agonists at the 5-HT1A receptor and are sometimes used in low doses as augmentations to standard antidepressants like the selective serotonin reuptake inhibitors (SSRIs).
[29] 5-HT1A receptor activation likely plays a significant role in the positive effects of serotonin releasing agents (SRAs) like MDMA (commonly known as ecstasy) as well.
[38] 5-HT1A receptor activation has been shown to increase dopamine release in the medial prefrontal cortex, striatum, and hippocampus, and may be useful for improving the symptoms of schizophrenia and Parkinson's disease.
[40][41][42] Enhancement of dopamine release in these areas may also play a major role in the antidepressant and anxiolytic effects as seen upon postsynaptic activation of the 5-HT1A receptor.
[46] Conversely, the 5-HT1A antagonist, WAY100635, alleviated learning and memory impairments induced by glutamate blockade (with dizocilpine)[47] or hippocampal cholinergic denervation (by fornix transection)[48] in primates.
Furthermore, 5-HT1A receptor antagonists such as lecozotan have been shown to facilitate certain types of learning and memory in rodents, and as a result, are being developed as novel treatments for Alzheimer's disease.
[69] For this reason, serotonin reuptake inhibitors that also have 5-HT1A receptor antagonistic or partial agonistic properties, such as vilazodone and SB-649,915, are being investigated and introduced as novel antidepressants with the potential for a faster onset of action and improved effectiveness compared to those currently available.
In contrast to SRAs, SSRIs may decrease serotonin levels initially (especially at lower dosages due to the biphasic mode of action mentioned above) and require several weeks of chronic dosing before serotonin concentrations reach their maximal elevation (due to 1A autoreceptor desensitization) and full clinical benefits for conditions such as depression and anxiety are seen[73][74] (although other studies show an acute increase in 5-HT[75][76] which may account for initial worsening of symptoms in sensitive individuals[77]).
For these reasons, selective serotonin releasing agents (SSRAs) such as MDAI and MMAI have been proposed as novel antidepressants with a putatively faster onset of action and improved effectiveness compared to current treatments.
[79] Another PET study found a negative correlation between the amount of 5-HT1A binding in the raphe nuclei, hippocampus and neocortex and a self-reported tendency to have spiritual experiences.