The putative lithium-mimetic ebselen reduces impulsivity in rodent models

Area of Science:

• Neuroscience
• Psychopharmacology
• Behavioral Science

Background:

• Impulse control deficits are common in psychiatric disorders like bipolar disorder, suicidality, and addictions.
• Lithium is used to lower impulsivity but has significant adverse effects and a low therapeutic index.
• Ebselen, a neuroprotective agent with a good safety profile, inhibits inositol monophosphatase (IMPase), a potential mechanism for lithium's effects, and reduces 5-HT_2A receptor function.

Purpose of the Study:

• To investigate the effects of ebselen on impulsive behavior in established rat models.
• To determine if ebselen's anti-impulsive effects are mediated by 5-HT_2A receptor inhibition.
• To assess ebselen's potential as a therapeutic agent for impulse control disorders.

Main Methods:

• Ebselen was tested in the five-choice serial reaction time task (5-CSRTT) and the rodent gambling task (rGT).
• These tasks model motor impulsivity (premature responses) and choice impulsivity (decision-making).
• Effects were measured at doses that reduced 5-HT_2A receptor function, with comparisons to a 5-HT_2A antagonist.

Main Results:

• Ebselen significantly decreased premature responses in the 5-CSRTT, indicating a reduction in motor impulsivity.
• This effect was observed both with and without cocaine administration.
• In the rGT, ebselen tended to reduce premature responding but did not affect choice behavior, suggesting a preferential effect on motor impulsivity.

Conclusions:

• Ebselen preferentially reduces motor impulsivity over choice impulsivity.
• Inhibition of 5-HT_2A receptor function appears to be a key mechanism underlying ebselen's anti-impulsive effects.
• These findings support the repurposing of ebselen as an anti-impulsive treatment for conditions characterized by poor impulse control.