102. Enriched maternal care decreases opioid self-administration in adulthood and alters neuroimmune signaling in the nucleus accumbens

Abstract

Despite decades of progress, the biological mechanisms underlying addiction are unknown. Glia, including astrocytes and microglia, profoundly influence neuronal function and may play a critical role in the development of drug addiction. Previously, we have shown that a neonatal handling procedure (which promotes enriched maternal care) reduces glial activation to an acute morphine challenge and prevents reinstatement of morphine conditioned place preference; likewise, similar results were obtained by pharmacological manipulation of glia within the nucleus accumbens (NAc). Here, we investigated the effects of opioid self-administration on central immune signaling within the NAc and its modulation by early-life experience. Male rat pups were handled (15 min/day) from postnatal day (P) 2 to P20 or left undisturbed. In adulthood, all rats were tested for self-administration of intravenous remifentanil (a short-acting opioid) in daily 1 h sessions for 2 weeks. Brains were then collected to examine persistent alterations in glial activation. Neonatal handling reduced acquisition of remifentanil; this effect was specific for opioids, as acquisition of food reward was unaffected. Remifentanil self-administration substantially increased glial antigen expression (Iba1 and GFAP) and proinflammatory gene expression in NAc, including the innate immune receptor TLR4. However, only handled rats showed increased expression of the anti-inflammatory cytokine IL-10. These data establish neural–glial interactions in the NAc as an essential component of self-motivated drug acquisition that can be altered by early-life environmental conditions.