Future directions for monitoring and human health research for the Arctic Monitoring and Assessment Programme.

For the last two and a half decades, a network of human health experts under the Arctic Monitoring and Assessment Program (AMAP) has produced several human health assessment reports. These reports have provided a base of scientific knowledge regarding environmental contaminants and their impact on human health in the Arctic. These reports provide scientific information and policy-relevant recommendations to Arctic governments. They also support international agreements such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the Minamata Convention on Mercury. Key topics discussed in this paper regarding future human health research in the circumpolar Arctic are continued contaminant biomonitoring, health effects research and risk communication. The objective of this paper is to describe knowledge gaps and future priorities for these fields.

Nutritionally small-for-dates rats: their subsequent growth, regional brain 5-hydroxytryptamine turnover, and behavior.

Rats were subjected to nutritional growth retardation either from conception to 5 postnatal days of age (fetal and neonatal restriction (FNR) group), or from 5 to 25 postnatal days of age (infantile restriction (IR) group). The FNR group may serve as a model for the human small-for-dates baby. At 20 weeks of age cerebellum, midbrain, and cerebrum were significantly reduced in weight by 4%, 5%, and 4%, respectively, in FNR animals when compared with controls. Only cerebellum and midbrain were affected in IR rats of the same age, but in both regions the percentage deficits (8% and 9%, respectively) were greater than in FNR animals. Both cerebellum and midbrain weighed significantly less in IR than in FNR rats. The timing of nutritional growth retardation appeared to be of little consequence to the regional brain turnover of 5-hydroxytryptamine in adulthood. The rate of synthesis in the hippocampus of both FNR and IR animals was significantly faster (67% and 75% respectively) than in controls. The increased turnover could perhaps represent "overactivity" of those 5-hydroxytryptaminergic neurons terminating in the hippocampus. Some differences in the behavior of the previously undernourished adult animals were also evident. On the fifth day of testing, control rats were most venturesome in the open field. Eighteen control rats left the edge zone within 2 min, whereas only 8 FNR and 11 IR rats did so. Most animals froze immediately after a 7-sex exposure to a loud electric bell. The delay before moving about again differentiated the three groups. FNR rats took longest to move out of the area in which they froze.

A comparison of the effects of cytosine arabinoside and adenine arabinoside on some aspects of brain growth and development in the rat.

1. Treatment of pregnant rats with cytosine arabinoside (ara-C, 50 mg/kg, i.p.)at 14 days of gestation severely impaired both prenatal and postnatal whole brain growth in their offspring, although the cerebellum was relatively less affected than whole brain. 2. Rats treated at 5 days of age with ara-C (250 mg/kg, i.p.) showed an impairment in growth of the cerebellum relative to the rest of the brain. 3. Adenine arabinoside (ara-A) treatment, either prenatally or postnatally, had negligible effect on brain growth, even at doses considerably higher than those of ara-C. 4. Adult rats, previously treated with ara-C (50 mg/kg, i.p.) at 14 days of gestation, showed an impairment in discrimination learning when tested in a water T-maze. 5. These results are discussed in relation to the proposed use of ara-C or ara-A as antiviral agents, particularly against intrauterine infection with cytomegalovirus.

Maze learning by adult rats after inhibition of neuronal multiplication in utero.

Rats whose mothers received hydroxyurea (HU, 1 or 2 g/kg) at 14 days of gestation had a 30% deficit in both brain and body weight at birth, when compared with controls. Number of brain cells at birth (mainly neurons) was reduced by 33-34%. A severe reduction in postnatal whole brain growth (31-33% in adulthood) was observed, but the cerebellum was relatively spared. In the Hebb-Williams maze text in adulthood HU animals made 28% more errors than controls over 12 problems. The differences were much more marked on certain problems and for HU animals with particularly small brains. In a T-maze spatial discrimination test in adulthood HU rats learned the initial response normally but, when required to reverse this response, showed a significant tendency to make more perseverative errors than controls.