Dissociating the long-term effects of fetal/neonatal iron deficiency on three types of learning in the rat.

Iron deficiency (ID) is a common nutrient deficiency worldwide. This condition is linked to changes in myelin formation, dopaminergic function, and energy metabolism. Early ID results in persistent long-term cognitive and behavioral disturbances in children, despite a return to normal iron status. The present study assesses formerly ID adult rats on maze learning tasks that depend on specific brain regions related to learning, specifically the hippocampus, striatum, and amygdala. Rat dams were fed ID chow starting on gestational Day 2 through postnatal Day 7, and behavioral testing began at postnatal Day 65--following a return to normal iron status. Formerly ID rats exhibited delayed acquisition of the hippocampus-dependant task and no differences from controls on the striatum- and amygdala-dependent tasks. These findings likely reflect long-term reduction in but not abolition of hippocampus-dependent learning and preserved function in other brain structures (e.g., striatum and amygdala).

Lead exposure alters the development of agonistic behavior in golden hamsters.

We tested the effects of exposure to different doses of lead acetate (either 0, 25, 100, or 400 ppm) on the development of aggressive behavior in male golden hamsters. Pups were tested for offensive responses across puberty, as they were maturing from play fighting to adult aggression. Our data show a dose-specific effect of lead exposure on the development of aggression during puberty at doses resulting in blood levels well below 20 microg/dl. Animals exposed to 25 ppm lead acetate were faster and performed more than twice as many attacks on intruders by late puberty. They were also twice as likely to initiate adult instead of play-fighting attacks around mid-puberty. These observations were independent of any effect on growth. Thus, exposure to low doses of lead enhanced aggression and accelerated its maturation. As such, our data support the association between exposure to low doses of lead and aggressive behavior in boys.

Glucose regulation of memory for reward reduction in young and aged rats.

Although baseline blood glucose levels in aged Fischer-344 rats are comparable to those of young rats, the rise in blood glucose in response to training-related stress is substantially attenuated. The diminished response may contribute to increased depletion of extracellular brain glucose levels during training in aged rats; the depletion is blocked and memory is enhanced by systemic injections of glucose. The present experiment examined the role of glucose in regulating memory for reward reduction training. Blood glucose levels exhibited a significant rise after reward reduction trials in young adult but not 2-year-old rats. Although young and aged rats exhibited comparable learning during the day of reward reduction training, aged rats exhibited more rapid forgetting of the learning response. Post-training glucose injections (200 mg/kg, i.p.) facilitated memory formation and slowed the rate of forgetting in young and old rats, consistent with the view that deficiencies in circulating glucose responses to training may contribute to the rapid forgetting evident in aged Fischer-344 rats.

Mnemonic functions of dorsal striatum and hippocampus in aversive conditioning.

These experiments examined the mnemonic functions of hippocampus and dorsal striatum in Pavlovian aversive conditioning. Rats were trained in a single session by presenting three paired tones and footshocks. Immediately after training, they were given microinjections of D-amphetamine or vehicle into either dorsal hippocampus or dorsal striatum. Twenty-four hours later conditioned freezing (measured as cessation of movement by infrared motion detectors) to the experimental context and to the tone were measured separately. Compared to vehicle injections, amphetamine injections into dorsal hippocampus significantly increased conditioned freezing to the context but not to the tone. Injections into dorsal striatum increased conditioned freezing to both the context and the tone. These results converge with findings from lesion experiments suggesting that hippocampus is involved in aversive conditioning with contextual CSs only, and that dorsal striatum is involved in aversive conditioning with both contextual and discrete cue CSs. The functions of the these two structures in relation to that of the amygdala in the mediation of conditioned freezing are discussed.

Lead and conditioned fear to contextual and discrete cues.

Male Fischer 344 rats received either tap water or water containing 250 ppm lead for 90 days prior to training in either Pavlovian fear conditioning or consummatory contrast, an aversive reward reduction paradigm. In Experiment 1, lead-exposed and -unexposed rats were trained in operant chambers over a 6-min session. After 3 min elapsed, three tone-shock pairings were presented over the remainder of the session. Rats then received 7 days of extinction training in an identical procedure with only tones presented, no shocks. Lead-exposed rats exhibited greater behavioral suppression to both the contextual and auditory cues that predicted shock. In Experiment 2, rats were placed in operant chambers daily and allowed to consume either a 15% or a 5% fructose solution for 7 days. On Day 8, the rats consuming the 15% fructose solution were shifted to the 5% solution for 3 days. Lead-exposed rats did not differ from their controls in either initial consumption of either solution or in the suppression of their consumption after shifting to the 5% solution. Taken together, these findings suggest that lead impairs the extinction of fear conditioning and this finding is not due to a nonspecific increase in aversive emotionality.

Lead and spatial vs. cued open field performance.

Male Fischer 344 rats received chronic exposure to either water containing 250 ppm lead or tap water. On the first day of the study, rats were allowed to habituate to a 1-m(2) open field arena with a rectilinear grid pattern of food wells on the floor for a 2-min session. On the following 7 days, half the rats were trained (four trials per day, 2-4-min intertrial interval) to find a food location based on extra-maze spatial cues and the other half were trained to find a food location based on a discrete intra-maze cue placed over the baited food well. While lead did not appear to significantly affect motor activity during the habituation phase, lead-exposed spatially trained rats exhibited superior acquisition and performance of the food-rewarded task compared to their controls and their cue-trained lead-exposed and counterparts. Furthermore, by the last day of training, Day 7, lead significantly reduced the relative amount of time spent on the periphery of the maze in spatially and cued-trained rats.