Prenatal methamphetamine exposure in Sprague-Dawley rats: Physical, behavioral and neurochemical outcomes

Methamphetamine (METH) abuse is increasing in the United States at an alarming rate, yet there remains a paucity of information concerning its effects on pregnant women and their offspring. Four experiments were designed to assess the manner by which METH-treatment affects the health and behavior of rat dams during pregnancy and after parturition, as well as the health, behavior, and brain dopamine content of drug-exposed offspring. Results from Experiment 1 indicate that gravid rats exposed to METH demonstrated a higher incidence of health problems and mortality as compared to pair-fed/saline-injected (PFS) or non-treated (NT) control group animals. Prenatal treatment of offspring significantly influenced postnatal maternal behavior of surrogate dams. Female rats with fostered, METH-treated offspring engaged in significantly more active crouch than did surrogate mothers with PFS or NT litters.^ Experiment 2 was designed to explore the potential toxicity and teratogenicity of prenatal METH administration in exposed offspring. Prenatal methamphetamine exposure resulted in a significant decrease in litter size and birth weight. One of the most worrisome findings of this investigation was that transplacental METH-exposure resulted in a dramatic increase in the incidence of perinatal complications. Throughout pre-weanling development, METH-exposed litters demonstrated persistent weight deficits as compared to NT and PFS pups. Both METH- and PFS-treated offspring exhibited accelerated acquisition of the surface righting reflex, while only METH-exposed pups demonstrated accelerated acquisition of the free-fall righting reflex.^ The manner by which prenatal exposure to methamphetamine affected subsequent social behavior in juvenile rats was explored in Experiment 3. Gestational exposure to a moderate dose of methamphetamine did not significantly influence the playful or non-playful social activity of juvenile rats. The effect of in utero METH-exposure on postnatal levels of brain dopamine (DA) in offspring was assessed in Experiment 4. Although not statistically significant, METH-treated offspring demonstrated higher levels of DA in striatum than NT pups. Taken together, the results from these experiments indicate that methamphetamine exposure during pregnancy is detrimental to the health of mothers and their offspring. In particular, METH-treated rat pups demonstrate both immediate and longer-term deleterious effects after in utero drug exposure.