Dahl salt-sensitive and salt-resistant rats: examination of learning and memory performance, blood pressure, and the expression of central nicotinic acetylcholine receptors.
Substantial human and animal data suggest a correlation between hypertension and memory impairment that may appear prior to overt manifestations of cerebrovascular pathology. It is unclear, however, whether hypertension plays a causal role in these memory deficits, whether hypertension and cognitive impairment are each based in family history and not interdependent, or whether a combination of these factors is important. The purpose of this study was to assess whether deficits in memory performance and nicotinic acetylcholine receptors were present in Dahl salt-sensitive rats (as observed previously in spontaneously hypertensive rats) and whether the presence of hypertension per se (induced with an 8% Na(+) diet) contributed to the deficits. Memory was assessed in a passive avoidance task, an eight-arm radial arm maze and in a water maze task, and nicotinic receptors were measured via quantitative receptor autoradiography utilizing [125I]alpha-bungarotoxin and [3H]epibatidine. Salt-sensitive rats exhibited impaired performance in both spatial learning tasks, but not the passive avoidance task, compared to controls (salt-resistant strain) and they exhibited reductions in nicotinic receptors labeled by [125I]alpha-bungarotoxin but not [3H]epibatidine in some brain regions, including some areas important for memory (e.g. the hippocampus and amygdala). In the radial arm maze, the degree of memory impairment and in binding studies the reduced expression of nicotinic receptors each failed to correlate with the highest blood pressures, and the salt-sensitive animals were impaired relative to controls whether or not the high Na(+) diet was administered. In contrast, higher blood pressures did correlate with inferior task performance in the water maze. These findings may suggest that the genetics of the subjects were critical for performance when appetitive drives were involved, but diet (and perhaps hypertension) were key to performance when memory did not involve appetitive drives or mechanisms. Overall, the data obtained from Dahl rats appear to support the role of family history (selective breeding in rats) as underlying the reductions in central nicotinic acetylcholine receptors, whereas both family history and hypertension may contribute to poor cognitive performance.
Program in Clinical and Experimental Therapeutics, University of Georgia College of Pharmacy, CJ-1020, Medical College of Georgia, Augusta, GA 30912, USA. artery@mail.mcg.edu
A V
AV
Terry
C M
CM
Hernandez
J J
JJ
Buccafusco
D000818:Animals; D001345:Autoradiography; D001362:Avoidance Learning / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism / Q000494:pharmacology; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D007457:Iodine Radioisotopes; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D018722:Nicotinic Agonists / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D020303:Rats, Inbred Dahl; D011978:Receptors, Nicotinic / Q000032:analysis / Q000378:metabolism*; D012982:Sodium, Dietary / Q000494:pharmacology; D013550:Swimming; D014316:Tritium; D014792:Visual Acuity / Q000502:physiology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D007457:Iodine Radioisotopes; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D012982:Sodium, Dietary; D014316:Tritium; C082748:epibatidine