Repeated 5-HT6 receptor activation facilitates flexible behavior in C57BL/6J mice

Area of Science:

• Neuroscience
• Pharmacology

Background:

• The serotonin 6 (5-HT6) receptor is a novel target for treating cognitive deficits in neuropsychiatric disorders.
• Research has primarily focused on 5-HT6 receptor antagonists, with limited understanding of agonist effects on behavior.

Purpose of the Study:

• To investigate the impact of the 5-HT6 receptor partial agonist EMD 386088 on behavioral flexibility.
• To assess the effects of EMD 386088 in an operant probabilistic reversal learning paradigm.

Main Methods:

• Female and male C57BL/6J mice were trained on a probabilistic discrimination task.
• Following criterion attainment, contingencies were reversed, and mice received EMD 386088 (1 or 5 mg/kg) or vehicle.
• Behavioral flexibility was assessed by measuring trials to reach reversal learning criterion.

Main Results:

• Mice treated with 1 mg/kg EMD 386088 reached the reversal learning criterion in significantly fewer trials than controls.
• The 5 mg/kg dose of EMD 386088 did not significantly affect reversal learning.
• Enhanced reversal learning at 1 mg/kg correlated with increased win-stay behavior, suggesting heightened sensitivity to reinforced trials.

Conclusions:

• The 1.0 mg/kg dose of EMD 386088 facilitates behavioral flexibility by enhancing reversal learning.
• Repeated activation of the 5-HT6 receptor may be beneficial for cognitive flexibility in neuropsychiatric disorders.