The effects of amphetamine on working memory and locomotor activity in adult rats administered risperidone early in life

Abstract

Antipsychotic drugs are used to manage symptoms of pediatric psychiatric disorders despite the relative absence of research regarding the long-term effects of these drugs on brain development. Using rats as a model, research has demonstrated that administration of the antipsychotic drug, risperidone, during early postnatal development elevates locomotor activity and sensitivity to the locomotor effects of amphetamine during adulthood. Because risperidone targets neurotransmitter receptors and forebrain regions associated with working memory, the present study determined whether early-life risperidone altered working memory during adulthood and its sensitivity to amphetamine-induced impairment. Female and male rats received subcutaneous (sc) injections of risperidone daily on postnatal days 14–42. Early-life risperidone increased spontaneous locomotor activity and amphetamine-induced hyperactivity during adulthood, although the effects were significantly greater in females. Working memory was tested in an operant-based, delayed non-matching-to-sample task. Early-life risperidone did not affect the percentage of correct choices observed during sessions with 0–8 second delays but impaired performance during sessions with 0–24 second delays. In a subsequent set of tests using 0–24 second delays, amphetamine (0.75 and 1.25 mg/kg, sc) significantly reduced the percentage of correct choices at most delays, but risperidone did not exacerbate this effect. These data suggest that early-life risperidone leads to modest deficits in working memory during adulthood, but does not alter the perturbation of working memory by amphetamine.

Amphetamine Modulation of Long-Term Object Recognition Memory in Rats: Influence of Stress

“…The psychostimulant properties of amphetamine depend on its modulation of both the noradrenergic and dopaminergic systems ( Fleckenstein et al, 2007 ). Amphetamine regulation of memory processes has been studied for many decades ( Martinez et al, 1983 ; Oscos et al, 1988 ; Bardgett et al, 2019 ). It has been shown that amphetamine-dependent enhancement of memory consolidation depends on the noradrenergic system stimulation properties ( Lee and Ma, 1995 ).…”

“…Literature data demonstrated that amphetamine induces profound effects on learning and memory processes. While it generally enhances memory consolidation, it has been shown that it increases memory retrieval errors and alters working memory performances ( Martinez et al, 1980a ; Ballard et al, 2014 ; Bardgett et al, 2019 ). Interestingly, it has been shown that amphetamine effects on memory consolidation are dependent on the amphetamine-induced activation of the noradrenergic system ( Lee and Ma, 1995 ; Colucci et al, 2019 ), a neurotransmitter system critically involved in the modulation of long-term memory consolidation ( Ferry et al, 1999 ; Roozendaal and McGaugh, 2011 ; McLumiere et al, 2017 ).…”