Methamphetamine (MA) is an illicit synthetic psychostimulant drug, and its abuse is growing worldwide. MA has been reported as the primary drug of choice, by drug-abusing women, during pregnancy. Since MA easily crosses the placental barrier, the fetus is exposed to MA in a similar fashion to the mother. This study aimed to evaluate the effect of long-term perinatal stressors and drug exposure on anxiety-like behavior in adult male rats using the open field test (OF) and elevated plus maze (EPM). Dams were divided into three groups according to drug treatment during pregnancy: controls (C), saline-SA [subcutaneous (s.c.), 1 ml/kg], and MA (s.c., 5 mg/kg). Litters were divided into four groups according to postnatal stressors: non-stressed controls (N), maternal separation (S), maternal cold water stress (W), and maternal separation plus maternal cold water stress (SW). Forty-five minutes before testing (in both OF and EPM), one-half of adult male rats received an (s.c.) injection of MA and the other half received an SA injection. Prenatal MA/stress exposure did not affect anxiety-like behavior in adult male rats in both tests. In the OF, an acute MA dose in adulthood increased the time spent in the central disk area, decreased time spent in the corners, and decreased time spent immobile and grooming. Also, postnatal stress increased time spent in the central disk area, decreased time spent in corners, and increased mobility compared to controls. All groups of rats exposed to postnatal stressors spent significantly less time in the closed arms of the EPM compared to controls. Overall, our results indicate that early postnatal stress and a single acute MA administration in adulthood decreases the parameters of anxiety-like behavior in adult male rats regardless of prenatal MA exposure. Moreover, postnatal stress via maternal separation impacts the effect of acute MA administration in adulthood. Long-term postnatal stress may thus result in improved adaptation to subsequent stressful experiences later in life.

• Keywords
• anxiety, elevated plus maze, maternal separation, methamphetamine, open field, postnatal stress, prenatal stress,
• Publication type
• Journal Article MeSH

The present study was aimed at evaluating cognitive changes following neonatal methamphetamine exposure in combination with repeated treatment in adulthood of female Wistar rats. Pregnant dams and their pups were used in this study. One half of the offspring were treated indirectly via the breast milk of injected mothers, and the other half of pups were treated directly by methamphetamine injection. In the group with indirect exposure, mothers received methamphetamine (5 mg/ml/kg) or saline (1 ml/kg) between postnatal days (PD) 1-11. In the group with direct exposure, none of the mothers were treated. Instead, progeny were either: (1) treated with injected methamphetamine (5 mg/ml/kg); or (2) served as controls and received sham injections (no saline, just a needle stick) on PD 1-11. Learning ability and memory consolidation were tested on PD 70-90 in the Morris Water Maze (MWM) using three tests: Place Navigation Test, Probe Test, and Memory Recall Test. Adult female progeny were injected daily, after completion of the last trial of MWM tests, with saline or methamphetamine (1 mg/ml/kg). The effects of indirect/direct neonatal methamphetamine exposure combined with acute adult methamphetamine treatment on cognitive functions in female rats were compared. Statistical analyses showed that neonatal drug exposure worsened spatial learning and the ability to remember the position of a hidden platform. The study also demonstrated that direct methamphetamine exposure has a more significant impact on learning and memory than indirect exposure. The acute dose of the drug did not produce any changes in cognitive ability. Analyses of search strategies (thigmotaxis, scanning) used by females during the Place Navigation Test and Memory Recall Test confirmed all these results. Results from the present study suggested extensive deficits in learning skills and memory of female rats that may be linked to the negative impact of neonatal methamphetamine exposure.

• Keywords
• Morris Water Maze (MWM), Wistar rat, methamphetamine, neonatal exposure, strategies,
• Publication type
• Journal Article MeSH