Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a...

Area of Science:

• Neuroscience
• Behavioral Science
• Pharmacology

Background:

• Chronic administration of the serotonin 1A and 7 receptors agonist 8-OH-DPAT induces compulsive checking and perseverative behavior, serving as an animal model for obsessive-compulsive disorder (OCD).
• Glutamate-modulating agents, including memantine and riluzole, have shown efficacy in clinical trials for various conditions, prompting investigation into their potential in OCD models.

Purpose of the Study:

• To evaluate the impact of 8-OH-DPAT on spatial learning in an animal model of OCD.
• To investigate the effects of co-administering memantine and riluzole on cognitive function and behavior in the 8-OH-DPAT-induced OCD model.

Main Methods:

• Rats were subjected to the active place avoidance task in a Carousel maze to assess spatial learning.
• 8-OH-DPAT was administered during habituation and/or acquisition phases.
• Rats received pretreatments with riluzole (1 mg/kg), memantine (1 mg/kg), or saline before acquisition sessions, followed by 8-OH-DPAT or saline injections.

Main Results:

• Repeated 8-OH-DPAT administration increased locomotion and impaired shock sector avoidance, indicating cognitive deficits.
• Discontinuing 8-OH-DPAT during acquisition negated its impact on learning.
• Memantine and riluzole significantly increased locomotion in 8-OH-DPAT treated rats; riluzole also increased entrances and decreased avoidance of the shock sector.

Conclusions:

• Monotherapy with glutamate-modulating agents (memantine, riluzole) exacerbates cognitive impairments in the 8-OH-DPAT animal model of OCD.
• These findings suggest that glutamate modulation may not be beneficial and could be detrimental for cognitive symptoms in OCD models.