Chronic risperidone administration leads to greater amphetamine-induced conditioned place preference.

Area of Science:

• Neuroscience
• Pharmacology
• Developmental Psychology

Background:

• Risperidone, an atypical antipsychotic, is increasingly prescribed for pediatric ADHD and conduct disorder.
• Developmental exposure to risperidone in rats is linked to altered adult locomotor activity and amphetamine sensitivity.

Purpose of the Study:

• To investigate the long-term effects of developmental versus adult risperidone administration on amphetamine's rewarding effects.
• To compare amphetamine-induced conditioned place preference (CPP) and locomotor activity following early-life or adult risperidone exposure.

Main Methods:

• Rats received chronic risperidone (3.0 mg/kg) during development (postnatal days 14-42) or adulthood (postnatal days 77-105).
• Locomotor activity and amphetamine CPP were assessed weeks after treatment cessation.
• Dopamine transporter (DAT) density in the forebrain was quantified in developmentally treated rats.

Main Results:

• Developmental risperidone exposure led to higher locomotor activity in female rats.
• Previous risperidone administration, particularly developmental, enhanced amphetamine CPP in both sexes.
• Reduced forebrain dopamine transporter density was observed in rats exposed to risperidone during development.

Conclusions:

• Chronic risperidone treatment during development alters adult locomotor activity and increases sensitivity to amphetamine's reinforcing properties.
• Decreased forebrain dopamine transporter density may underlie the heightened amphetamine sensitivity observed after developmental risperidone exposure.