The sensitivity of prenatal
protein malnourished rats to the amnestic properties of the direct GABAA receptor agonist
muscimol and the selective
benzodiazepine (BZ) receptor agonist,
CL218,872, was studied in the male offspring of rats provided with a
protein deficient diet (6%
casein) for 5 weeks prior to mating and throughout pregnancy. At postnatal day 90, rats were tested during acquisition of the submerged platform version of the Morris water maze task using four systemic doses of
muscimol (0.1, 0.3, 1.0 and 1.8 mg/kg i.p.) or three systemic doses of
CL218,872 (1.0, 3.2, and 5.6 mg/kg i.p.). In a dose dependent manner both drugs impaired acquisition of the task and impaired accuracy of the search pattern on the probe trial (platform removed). However, neither
drug dissociated the performance of the two nutritional groups. These data are important in light of previous findings of differential behavioral effects of the non-specific BZ agonist,
chlordiazepoxide (
CDP), on spatial learning and on
drug discrimination in prenatally malnourished rats and in the context of previous findings of reduced sensitivity to the
anxiolytic effects of non-specific BZ receptor agonists across a wide variety of models of
malnutrition. The present findings also support the concept that prenatal
malnutrition does not affect the global functioning of the GABAA receptor, but fundamentally alters the way in which a subset of GABAA receptors (i.e. those containing the alpha2, alpha3 and/or the alpha5 but not the alpha1 subunit) is modulated by BZs.