Acute serotonin 2A receptor activation impairs behavioral flexibility in mice

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• Serotonin 2A (5-HT_2A) receptors are key targets for hallucinogens and antipsychotics.
• 5-HT_2A receptor function is linked to executive functions, including behavioral flexibility.
• Previous research indicated 5-HT_2A receptor blockade enhances behavioral flexibility in disease models.

Purpose of the Study:

• To investigate the impact of acute 5-HT_2A receptor activation on behavioral flexibility.
• To examine the effects of selective 5-HT_2A and mixed 5-HT_2A/2C agonists on reversal learning.
• To explore the interaction between 5-HT_2A and 5-HT_2C receptors in modulating behavioral flexibility.

Main Methods:

• Male C57BL/6 J mice were administered DOI (5-HT_2A/2C agonist) or 25CN-NBOH (selective 5-HT_2A agonist).
• Behavioral flexibility was assessed using a probabilistic spatial discrimination and reversal learning task.
• The study included experiments with a 5-HT_2C receptor antagonist (SER-082) alone and in combination with DOI.

Main Results:

• While DOI alone did not affect reversal learning, 25CN-NBOH significantly impaired it.
• Combined treatment with SER-082 and DOI worsened reversal learning performance.
• Locomotor activity was not affected by the tested dose of 25CN-NBOH.

Conclusions:

• Acute activation of 5-HT_2A receptors impairs probabilistic reversal learning in male mice.
• 5-HT_2A and 5-HT_2C receptors appear to have opposing influences on behavioral flexibility.
• These findings contribute to understanding the complex role of serotonin receptors in cognition.