Exploring the spectrum of heroin-induced changes in the rat brain.

Abstract

The primary objective of this study was to investigate the effects of prolonged heroin exposure on adult male rats. Our findings demonstrate that this intervention induces deficits in memory, synaptic plasticity, emotional regulation, and motor function. These impairments appear to be associated with reduced levels of BDNF, increased expression of REST/NRSF, and elevated astrocyte activity within the hippocampus. We employed a multimodal approach to assess the impact of heroin in 24 adult male rats following 2 weeks of daily injections. Behavioral assessments were conducted to evaluate memory and anxiety-like and depression-like behaviors, followed by tests of neuromuscular and locomotor function. Molecular and histological analyses were subsequently performed to characterize heroin-induced alterations in the brain. Heroin-treated rats showed impaired performance in cognitive tasks, evidenced by reduced scores in the Y-maze and shuttle box tests. Furthermore, heroin exposure negatively affected behavioral scores in the open field test, tail suspension test, and elevated plus maze. Electromyography (EMG) revealed increased latency, indicating disruptions in neuromuscular activity. Indicators of long-term potentiation (LTP), including population spike amplitude, and field EPSP slope, were significantly reduced following heroin administration. Immunohistochemical analysis revealed marked astrogliosis and alterations in BDNF and REST expression in the CA1 region of the hippocampus. Additionally, heroin disrupted the spatial organization of neurons. In conclusion, these results suggest that heroin exposure induces structural and functional neuronal changes, likely mediated by neuroinflammation and dysregulated neurotrophic signaling, which may underlie the observed cognitive impairments.