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Delayed yet persistent effects of daily risperidone on activity in developing rats.

Rachel M Stevens¹, Matthew A Gannon, Molly S Griffith

¹Department of Psychological Science, Northern Kentucky University, Highland Heights, Kentucky, USA.

Behavioural Pharmacology

|March 10, 2016

Summary

Early risperidone (antipsychotic drug) treatment in young rats caused delayed hyperactivity that persisted after stopping the drug, unlike in adult rats. This highlights developmental differences in drug response.

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Area of Science:

Neuroscience
Developmental Pharmacology
Behavioral Pharmacology

Background:

Risperidone is a widely used antipsychotic medication in pediatric populations.
Early-life exposure to certain medications can have long-lasting effects on behavior.
Understanding the developmental trajectory of drug-induced behavioral changes is crucial for pediatric treatment.

Purpose of the Study:

To investigate the emergence and persistence of elevated locomotor activity following developmental exposure to risperidone in rats.
To compare the time course of behavioral changes induced by risperidone in developing versus adult rats.
To determine if hyperactivity induced by early-life risperidone administration persists after drug cessation.

Main Methods:

Rats were administered daily injections of risperidone (1.0 and 3.0 mg/kg) or vehicle for 4 weeks, starting at postnatal days 14 (developing) and 74 (adult).

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Locomotor activity was measured immediately after injection, 20 minutes before the next daily injection, and 1 week after the final injection.

Behavioral data were analyzed to compare activity levels between risperidone-treated and vehicle-treated groups across different age points and sexes.

Main Results:

Risperidone acutely decreased locomotor activity in both developing and adult rats.
Adult rats showed compensatory hyperactivity within 24 hours of the first risperidone dose.
Developing rats exhibited delayed compensatory hyperactivity, emerging in the fourth week of treatment, and this hyperactivity persisted after drug cessation, particularly in females.

Conclusions:

The emergence of compensatory hyperactivity during long-term antipsychotic drug administration is delayed in developing rats compared to adults.
Early-life exposure to risperidone can induce persistent behavioral changes that outlast the treatment period.
Developmental stage significantly influences the onset and persistence of behavioral side effects from antipsychotic medications.