PRENATALLY MALNOURISHED FEMALE BUT NOT MALE RATS SHOW INCREASED SENSITIVITY TO MK-801 IN A DIFFERENTIAL REINFORCEMENT OF LOW RATES TASK

A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and cholinergic systems has previously been iden tified in predominantly male malnourished animals. The present study s ought to compare the effects of the non-competitive N-methyl-D-asparta te (NMDA) receptor antagonist MK-801 on responding maintained by a dif ferential reinforcement of low rates (DRL-18 s) operant schedule in tw o groups of rats with different prenatal nutritional histories (well-n ourished and protein restricted). The schedule required that the rats space their responses at least 18 s apart in order to obtain food rein forcement (timing behavior). After training to a stable high proficien cy, MK-801 was administered to female rats (Experiment 1) at doses of 0 (saline), 0.004, 0.008, 0.016, 0.024 or 0.032 mg/kg (doses expressed as the free-base). MK-801 produced dose-dependent decreases in the pe rcentage efficiency of responding and the number of rewarded responses , with dose-dependent increases in the number of responses emitted. Pr enatal malnutrition significantly shifted the inter-response time (IRT ) curve to the left, relative to that of the well-nourished controls, leading to a significantly lower efficiency and a lower number of rein forcers, at an MK-801 dose of 0.016 mg/kg. In Experiment 2, the effect of MK-801 on DRL performance was compared between male and female rat s after prenatal malnutrition. In general, females proved more sensiti ve to MK-801 than males. Consistent with Experiment 1, a significantly greater drug impairment was observed in prenatally malnourished femal es compared with well-nourished females, albeit at a slightly higher d ose (0.032 mg/kg). Prenatal malnutrition did not alter the drug respon se in male rats. These findings suggest that the behavioral response t o NMDA blockade is augmented in adult female, but not male, rats after prenatal malnutrition.