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Postnatal cocaine exposure affects neonatal passive avoidance performance and cholinergic development in rats
1Section of Behavioral Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
Insights
Neonatal cocaine exposure in Wistar rats caused minor learning deficits and decreased cholinergic enzymes in the septum. These findings suggest early-life cocaine impacts brain development and function.
Area of Science:
- Neuroscience
- Developmental Toxicology
- Neuropharmacology
Background:
- Neonatal exposure to psychostimulants like cocaine can impact neurodevelopment.
- Cholinergic systems are crucial for learning and memory processes.
- The effects of early-life cocaine exposure on the developing cholinergic system are not fully understood.
Purpose of the Study:
- To investigate the long-term effects of neonatal cocaine exposure on learning and memory in Wistar rats.
- To examine the impact of early-life cocaine exposure on cholinergic system integrity in the developing brain.
Main Methods:
- Wistar rat pups were administered cocaine hydrochloride (25 mg/kg) or saline subcutaneously from postnatal days 1-11.
- A passive avoidance task (step-off response with foot-shock) was used to assess learning and memory on postnatal days 12 (acquisition) and 13 (retention).
- Choline acetyltransferase (ChAT) enzymatic activity and neuronal immunoreactivity were analyzed in forebrain structures on postnatal day 13.
Main Results:
- Cocaine-treated rats exhibited slight deficits in the latency to step-off during acquisition.
- A generalized increase in trials to criterion was observed in the retention phase for cocaine-exposed rats.
- A decrease in cholinergic enzyme activity was found specifically in the septum of cocaine-treated subjects.
- Other basal forebrain cholinergic regions remained unaffected by neonatal cocaine exposure.
Conclusions:
- Neonatal cocaine exposure in Wistar rats leads to subtle but measurable deficits in passive avoidance learning and memory.
- The developing cholinergic system, particularly in the septum, is vulnerable to cocaine's neurotoxic effects during early life.
- These findings highlight the potential for long-term neurobiological consequences of early-life psychostimulant exposure.
Abstract:
Wistar rat pups received either cocaine HCl (25 mg/kg) or saline (0.9% NaCl) SC from postnatal days 1-11. On days 12 (acquisition) and 13 (retention), they underwent a passive avoidance task (step-off response; grid foot-shock at 0.35 mA). Slight deficits were found in cocaine-treated subjects for latency to step-off during acquisition and for generalized increase in the number of trials to criterion in retention. On postnatal day 13, the level of choline acetyltransferase (ChAT) enzymatic activity and the distribution of ChAT neuronal immunoreactivity in forebrain structures were examined. These morphometric and biochemical studies demonstrate a decrease of cholinergic enzymes in the septum, while the remaining basal forebrain cholinergic regions were unaffected.