Acute serotonin 1B/1A receptor activation impairs behavioral flexibility in C57BL/6J mice
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Published on: December 22, 2008
Brandon L Oliver1, McKenna H Burdette1, Alma E Pahua1
1California State University, San Bernardino, Department of Psychology, 5500 University Parkway, San Bernardino, CA 92407, USA.
Abstract:
Pharmacological activation of the serotonin (5-HT) 1B and 5-HT1A receptors has been shown to induce OCD-like perseverative circling and locomotor stereotypy in rodents. Although, several studies have examined how activation of these receptors facilitates these motor-associated OCD-like behaviors, it is not known how acute 5-HT1B and 5-HT1A activation impacts behavioral inflexibility, a common trait related to OCD. The current study examined how acute 5-HT1B/1A receptor agonist RU24969 treatment at 0.01, 0.1, and 1.0 mg/kg impacted behavioral flexibility in both female and male C57BL/6J mice. Behavioral flexibility was tested using a spatial reversal learning task, with probabilistic reward contingencies. In addition, locomotor activity and anxiety-like behaviors were also measured. RU24969 at 0.1 and 1.0 mg/kg impaired behavioral flexibility in both female and male C57BL/6J mice. RU24969 treatment at 1.0 mg/kg reduced locomotor activity in male mice, although RU24969 treatment did not significantly reduce locomotor activity in female mice. In the open field, 1.0 mg/kg elevated anxiety-like behavior in male mice only. Overall, these results demonstrate that acute 5-HT1B and 5-HT1A receptor activation leads to impairments in behavioral flexibility, a common trait associated with OCD.
Insights
Acute activation of serotonin (5-HT) 1B and 5-HT1A receptors impairs behavioral flexibility in mice. This finding is crucial for understanding obsessive-compulsive disorder (OCD) and developing targeted treatments.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Psychiatry
Background:
- Serotonin (5-HT) 1B and 5-HT1A receptor activation is linked to OCD-like motor behaviors in rodents.
- The impact of acute 5-HT1B/1A activation on behavioral inflexibility, a key OCD trait, remains understudied.
Purpose of the Study:
- To investigate the effects of acute 5-HT1B/1A receptor agonist RU24969 on behavioral flexibility in male and female mice.
- To assess the influence of RU24969 on locomotor activity and anxiety-like behaviors.
Main Methods:
- C57BL/6J mice (male and female) were treated with varying doses of RU24969 (0.01, 0.1, 1.0 mg/kg).
- Behavioral flexibility was assessed using a spatial reversal learning task with probabilistic reward contingencies.
- Locomotor activity and anxiety-like behaviors were measured using open field tests.
Main Results:
- RU24969 (0.1 and 1.0 mg/kg) significantly impaired behavioral flexibility in both sexes.
- Locomotor activity was reduced in males but not females at 1.0 mg/kg.
- Anxiety-like behavior was elevated in males at 1.0 mg/kg.
Conclusions:
- Acute 5-HT1B and 5-HT1A receptor activation leads to deficits in behavioral flexibility.
- These findings highlight the role of these serotonin receptors in cognitive traits relevant to OCD.
- Sex-dependent effects were observed for locomotor activity and anxiety.
