(+)‐Methamphetamine increases corticosterone in plasma and BDNF in brain more than forced swim or isolation in neonatal rats

Abstract

(+)‐Methamphetamine (MA) administered on postnatal days (P) 11–15 (four times/day) results in increased corticosterone that overlaps the stress hyporesponsive period (SHRP; P2–14) and leads to later learning and memory deficits. Elevated corticosterone during the SHRP results in neurotrophin changes and long‐term effects on learning. We determined whether two known stressors could mimic the effects of MA [10 (mg/kg)/dose] administration in neonatal rats. Stressors were four 15‐min sessions of forced swim or isolation (confinement in forced swim tubes without water). Saline and weighed‐only controls were included and all five treatments were represented within each litter. Corticosterone in plasma and brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in neostriatum and hippocampus were examined after one or four treatments on P11 or P15 (0.5, 1.75, 6.5, or 24 h after first dose). MA increased corticosterone and BDNF; forced swim and isolation also increased corticosterone, but to a lesser extent than MA, and neither stressor increased BDNF. NGF was unaffected by saline treatment, but there was a minor reduction in NGF in the forced swim group compared with the weighed‐only group. The data show that MA is more potent at releasing corticosterone and increasing BDNF than short‐term, repeated episodes of forced swim or isolation. The possible relationship between these changes and the long‐term cognitive effects of developmental MA administration are discussed. Synapse 62:110–121, 2008.