Stereotypy and spontaneous alternation in deer mice and its response to anti-adenosinergic intervention
Geoffrey de Brouwer1, Jaco Engelbrecht1, Daniel C Mograbi2,3
1Center of Excellence for Pharmaceutical Sciences, Department of Pharmacology, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.
Abstract:
Repetitive behavioral phenotypes are a trait of several neuropsychiatric disorders, including obsessive-compulsive disorder (OCD). Such behaviors are typified by complex interactions between cognitive and neurobiological processes which most likely contribute to the suboptimal treatment responses often observed. To this end, exploration of the adenosinergic system may be useful, since adenosine-receptor modulation has previously shown promise to restore control over voluntary behavior and improve cognition in patients presenting with motor repetition. Here, we employed the deer mouse (Peromyscus maniculatus bairdii) model of compulsive-like behavioral persistence, seeking to investigate possible associations between stereotypic motor behavior and cognitive flexibility as measured in the T-maze continuous alternation task (T-CAT). The effect of istradefylline, a selective adenosine A2A receptor antagonist at two doses (10 and 20 mg kg-1 day-1 ) on the expression of stereotypy and T-CAT performance in high (H) and non-(N) stereotypical animals, was investigated in comparison to a control intervention (six groups; n = 8 or 9 per group). No correlation between H behavior and T-CAT performance was found. However, H but not N animals presented with istradefylline-sensitive spontaneous alternation and stereotypy, in that istradefylline at both doses significantly improved the spontaneous alternation scores and attenuated the stereotypical expression of H animals. Thus, evidence is presented that anti-adenosinergic drug action improves repetitive behavior and spontaneous alternation in stereotypical deer mice, putatively pointing to a shared psychobiological construct underlying naturalistic stereotypy and alterations in cognitive flexibility in deer mice.
Insights
Istradefylline, an adenosine A2A receptor antagonist, reduced repetitive behaviors and improved cognitive flexibility in stereotypical deer mice. This suggests a link between naturalistic stereotypy and cognitive flexibility deficits in these animals.
Area of Science:
- Neuroscience
- Behavioral Science
- Pharmacology
Background:
- Repetitive behaviors are characteristic of neuropsychiatric disorders like OCD, often linked to complex cognitive and neurobiological factors.
- Suboptimal treatment responses in these disorders highlight the need for novel therapeutic targets, such as the adenosinergic system.
- Adenosine receptor modulation has shown potential in restoring behavioral control and improving cognition in individuals with motor repetition.
Purpose of the Study:
- To investigate the association between stereotypic motor behavior and cognitive flexibility in a deer mouse model.
- To examine the effects of istradefylline, a selective adenosine A2A receptor antagonist, on stereotypy and cognitive flexibility.
Main Methods:
- Utilized the deer mouse (Peromyscus maniculatus bairdii) model, differentiating between high (H) and non-stereotypical (N) animals.
- Assessed cognitive flexibility using the T-maze continuous alternation task (T-CAT).
- Administered istradefylline (10 and 20 mg/kg/day) or a control intervention to six experimental groups (n=8-9 per group).
Main Results:
- No correlation was found between high stereotypy behavior and T-CAT performance.
- Istradefylline significantly improved spontaneous alternation scores in H animals, indicating enhanced cognitive flexibility.
- Both doses of istradefylline attenuated the expression of stereotypy in H animals, while N animals showed no significant changes.
Conclusions:
- Anti-adenosinergic drug action, specifically with istradefylline, effectively improves repetitive behavior and spontaneous alternation in stereotypical deer mice.
- These findings suggest a shared psychobiological basis for naturalistic stereotypy and cognitive flexibility deficits.
- The adenosinergic system represents a potential therapeutic target for conditions characterized by repetitive behaviors and cognitive impairments.
