Effects of prenatal methamphetamine exposure on spatial cognition and hippocampal synaptic plasticity in adolescent rats.

Global rise in methamphetamine (MA) abuse during pregnancy has placed a large number of children at risk for the adverse consequences of prenatal methamphetamine exposure (PME). While behavioral and neurocognitive deficits of PME have been extensively studied in humans and adult rodents, far less is known regarding the sex- and dose-dependent effects of PME as well as the underlying mechanisms. Adolescence in nonhuman primates is also a less explored territory. In the present study, PME was inducted by oral treatment to pregnant rats on gestational days 15-19 with either low dose (0.1 mg/ml) or high dose (0.6 mg/ml) of MA. The cognitive effects of PME were then evaluated in two adolescence age-intervals: early adolescent (started on postnatal day [PND] 21) and mid-adolescent (started on PND 33), among male and female rat offspring using Morris water maze (MWM) test. Alterations in hippocampal synaptic plasticity in Schaffer collaterals-CA1 pathway were also measured in vitro. Results of behavioral test showed that PME led to serious deficits of learning and memory abilities in both male and female rat offspring. PME also depressed LTP in most of the PME subgroups. Moreover, 21-day-old rats were more sensitive to PME-induced cognitive impairment in MWM tasks, but not in hippocampal synaptic plasticity, than 33-day-old rats. No sex-dependent effects of PME were found on the cognitive function and synaptic plasticity. These findings confirmed that PME impacted negatively on cognitive performance in prepubertal male and female rats, and the impairment of hippocampal synaptic functions might partly play a significant role in these effects.