Antagonists are any chemicals that fit into receptor sites on the post-synaptic neuron, inhibiting the neuron from firing. Well-known antagonists for serotonin, which we looked at in the previous blog post, are anti-psychotic drugs like Clozapine, which acts on the HT2A serotonin receptors to decrease the effects of serotonin in the brain. Many ant-psychotic drugs also act as antagonists for dopamine, as an excess of both dopamine and serotonin has been associated with schizophrenia.
However, easy-to-understand studies referencing this effect of Clozapine are difficult to come by, so while this is useful knowledge for students on how anti-psychotic medication works, when teaching about antagonists there is more available research on the effects of scopolamine on acetylcholine, and hence on memory. (And incidentally on motion sickness, as scopolamine is excellent at preventing nausea and vomiting!)
Scopolamine acts by blocking the acetylcholine receptors, specifically the muscarinic receptors (see the link below). Atri et al (2004) reported how blocking the muscarinic acetylcholine receptors (mAChRs), by injecting scopolamine impairs learning of paired words.
As an age-related deterioration in cognitive function is thought to be predominantly related to a decline in cholinergic neurotransmission (relating to nerve cells in which acetylcholine acts as a neurotransmitter), scopolamine administration has often been used to model dementia. Scopolamine has therefore been extensively used for preclinical and clinical testing of treatments for cognitive impairment. For example, Tröster et al (2013) found that scopolamine negatively affected anterograde short-term memory and verbal and nonverbal learning in middle-aged men.
Biological psychology has come to the fore over the past years. The mapping of the human genome combined with improved brain-scanning techniques has meant that the biological correlation to psychological conditions is more easily identifiable, and it is clear that many mental disorders like major depressive disorder, anxiety disorders and schizophrenia are explainable through a gene x environment interaction. This usually means that an inherited genetic pre-disposition to a disorder, or a certain behaviour or addiction is triggered environmentally.
Talking of genes takes us to neurotransmitters. How? Genes make proteins which make neurotransmitters and genes also transport neurotransmitters across the synapse. (See Caspi et al._2003 and the 5HTTR serotonin transporter gene). Neurotransmitters are agonists –they bind with receptor sites on the post-synaptic neuron and cause an action potential. Drugs are also agonists that act in the same way, but they are not natural in our nervous system. Neurotransmitters are known as endogenous agonists (internal agonists); drugs, or any chemicals taken into the body, to deliberately stimulate a certain neurotransmitter or group of neurotransmitters, are exogenous agonists (external agonists).
An exogenous agonist for serotonin is MDMA (Ecstasy). It works by binding with the serotonin transporter genes and also with the receptor sites, temporarily increasing the serotonin in the synapse in the neocortex (part of the cerebral cortex), the amygdala, hippocampus and hypothalamus, affecting cognitions such as memory and perceptions, as well as mood. We party!
However, studies have suggested that there is a rebound effect, whereby damage to the serotonin transporters after several doses of MDMA over a period of a few days has resulted in an ultimate decrease of serotonin in the brain, and memory and mood impairment, leading to theories that this might be linked to a motivation to take more and eventually to possible addiction. (See McCann et al MDMA and memory).
Of course, the opposite to an agonist is…an antagonist, which will be the subject of the next blog post.