The association between drugs and behavior is a field of research that has been essential in prescription medicines. Drugs hold the ability to influence behavior in a number of different ways; therefore studies are required to investigate these influences. Iig, Enkel, Bartsch, and Bähner (2018) are four psychologists who were interested in examining the effects of a designer drug on the behavior of rats – a designer drug being a drug which is synthetically made to mimic the effects of other drugs. The antipsychotic drug clozapine was the designer drug of choice for the purposes of this experiment. Clozapine is a drug that contains clozapine-N-oxide (CNO), which in this case is the active ingredient in clozapine that will activate the designer drug receptors – i.e., the sites in the brain where the drug will bind to take action will be activated by clozapine. The drug fits into the receptors just as a key fits into a lock to open a door.
This experiment focused on multiple areas of behavior in rats to examine the effects of clozapine upon these behaviors. To test this, two groups of rats were recruited – one group had received a low dosage of clozapine and the other received an injection of a placebo – a saline injection which contained no active drugs. Both of the groups were tested on different measures that would indicate if the rats experienced any changes in behavior. The researchers were particularly interested in the effect that clozapine has on anxiety. To measure this behavior the experimenters set up a test called the elevated plus-maze. This test consists of a maze which was elevated 50cm off of the floor. There are four extended arms that are connected by a platform and the rats are placed individually onto this platform to roam freely and explore. Two of the arms are enclosed with small walls and the other two are open. Where the rat tends to stay in the maze is a good indicator of the anxiety level they’re experiencing.
An interesting finding with this study was that the group of rats who did not receive the drug had shown lesser levels of anxiety while in the elevated plus-maze. Rats who received clozapine exhibited more anxiety-related behaviors. The researchers went on to examine the effects clozapine has on the brain to look for a possible explanation. Serotonin, which is a neurotransmitter (a chemical that conveys messages in the brain), is responsible for mood regulation. Serotonin type 2A receptors – one of the locations in the brain where drugs will bind to have an effect on serotonin – were found to be affected when the rats were given clozapine. Clozapine was found to block the serotonin 2A receptors, which from previous research has already demonstrated that the blocking of this receptor is known to have an anxiety-inducing effect. Serotonin cannot reach the receptor and take action, leading to lower levels of serotonin which in turn leads to higher levels of anxiety.
In terms of other behaviors the experimenters measured, such as the impact on social interaction, no differences were found between the two groups of rats. This can be explained by the fact that clozapine acts on multiple receptors in the brain, not just the serotonin type 2A receptors. Clozapine binds to multiple receptors but has different effects depending on the receptor it is bound to. When it binds to the serotonin type 2A receptor, it binds loosely which yields an effective change on the chemistry behind that neurotransmitter. In other receptors, clozapine binds more tightly which has a lessened effect of the drug – the neurotransmitters that bind to that receptor tend to be unaffected or affected very minimally. This is why different types of behaviors vary when drugs are administered.
The results of this research study have an important implication in treating mental health disorders with medications. The results imply that in a patient who suffers from anxiety, it is not the smartest choice to prescribe clozapine. Clozapine in low dosages may not affect many other behaviors, but anxiety was observed to be induced by this drug.
Reference
Iig, A.K., Enkel, T., Bartsch, D., & Bähner, F. (2018). Behavioral Effects of Acute Systemic Low-Dose Clozapine in Wild-Type Rats: Implications for the Use of DREADDs in Behavioral Neuroscience. Frontiers in Behavioral Neuroscience, 12 (173), 1-10.