Neonatal Escherichia coli infection alters glial, cytokine, and neuronal gene expression in response to acute amphetamine in adolescent rats

Abstract

Neonatal bacterial infection in rats alters the responses to a variety of subsequent challenges later in life. Here we explored the effects of neonatal bacterial infection on a subsequent drug challenge during adolescence, using administration of the psychostimulant amphetamine. Male rat pups were injected on postnatal day 4 (P4) with live Escherichia coli (E. coli) or PBS vehicle, and then received amphetamine (15mg/kg) or saline on P40. Quantitative RT-PCR was performed on micropunches taken from medial prefrontal cortex, nucleus accumbens, and the CA1 subfield of the hippocampus. mRNA for glial and neuronal activation markers as well as pro-inflammatory and anti-inflammatory cytokines were assessed. Amphetamine produced brain region specific increases in many of these genes in PBS controls, while these effects were blunted or absent in neonatal E. coli treated rats. In contrast to the potentiating effect of neonatal E. coli on glial and cytokine responses to an immune challenge previously observed, neonatal E. coli infection attenuates glial and cytokine responses to an amphetamine challenge.

Figure 1

Gene expression in the mPFCof rats exposed on P4 to E. coli or PBS and to amphetamine or saline in adolescence. Adolescent amphetamine increased gene expression of IL-1β, IL-6, TNFα, CD200, and Arc, and this increase was absent or attenuated in neonatal E. coli treated rats. Data are normalized to a percent of each neonatal treatment group’s saline control. Values are means ± SEMs of 6 to 8 rats/group. ** Significantly different from all other groups, p < .01. * Significantly different from all other groups, p < .05. # Significantly different from PBS + saline, p < .05.

Figure 2

Gene expression in the NAcc of rats exposed on P4 to E. coli or PBS and to amphetamine or saline in adolescence. Adolescent amphetamine increased gene expression of IL-1β and CD200, and this increase was attenuated or reversed in neonatal E. coli treated rats. Data are normalized to a percent of each neonatal treatment group’s saline control. Values are means ± SEMs of 5 to 8 rats/group. * Significantly different from all other groups, p < .05. # Significantly different from saline-injected rats within same neonatal group, p < .05.

Figure 3

Gene expression in the CA1 region of the hippocampus of rats exposed on P4 to E. coli or PBS and to amphetamine or saline in adolescence. Adolescent amphetamine increased gene expression of GFAP and Arc, and this increase was absent in neonatal E. coli treated rats. Data are normalized to a percent of each neonatal treatment group’s saline control. Values are means ± SEMs of 6 to 8 rats/group. * Significantly different from all other groups, p < .05.