Behavioral, endocrine, and neurochemical effects of sulfomucopolysaccharide treatment in the aged Fischer 344 male rat.

1. Daily treatment of male 19- to 22-month-old Fischer 344 male rats with Ateroid (20 mg/kg/day, p.o.), beginning one month before and continuing throughout testing, resulted in a significant partial reversal of age-related deficits in: a) Conditioned one-way (spatial, unsignaled) avoidance acquisition and retention b) Conditioned two-way (nonspatial, signaled) avoidance acquisition. 2. Ateroid reversed the age-related reductions in nucleus accumbens DOPAC and HVA levels, but not the age-related decrease in neostriatal HVA content or concomitant increase in 5-HIAA levels. Reduced dopamine turnover in the nucleus accumbens may underlie, at least in part, age-related deficits in conditioned avoidance learning and retention. Thus, the behavioral effects of Ateroid observed in the present study may be due to its normalizing influence on dopamine neurotransmission in the nucleus accumbens. 3. Stress-induced corticosterone secretion was greater in the old than in the young vehicle-treated rats. Ateroid treatment normalized this exacerbated corticosterone response to stress. 4. Daily Ateroid treatment did not affect any of the parameters measured in the young (5-8 months) F344 male rats. 5. Ateroid treatment did not affect the age-related reductions in exploratory behavior. The aged and young animals did not differ in their swimming ability. Thus, the effect of Ateroid on learning and memory processes does not appear to be due to an effect on locomotor or performance skills. 6. The age-related deficits in conditioned avoidance learning were not associated with abnormal basal (morning trough) plasma corticosterone levels, and Ateroid did not affect basal plasma corticosterone concentrations.

Neurochemical, endocrine and immunological responses to stress in young and old Fischer 344 male rats.

Two experiments were performed. In the first, a 20 min conditioned emotional response (CER) paradigm was used to compare the neurochemical, endocrine and immunological responses to stress of 7- and 22-month-old Fischer 344 (F344) male rats. In the second, corticosterone levels 20 min following ether stress, and regional brain type I and II corticosterone receptor densities were examined using 7- and 17.5-month-old F344 male rats. Dopamine (DA) metabolism in old nonstressed rats was significantly reduced in the medial frontal cortex, neostriatum, nucleus accumbens and hypothalamus, but not in the amygdala. The CER procedure, nevertheless, increased medial frontal cortical, nucleus accumbens and amygdaloid DA turnover in both the young and old rats. The young and old nonstressed rats did not evidence differences in norepinephrine (NE) and serotonin (5-HT) concentrations. However, stress resulted in a decrease in medial frontal cortical 5-hydroxyindoleacetic acid (5-HIAA) and hypothalamic 5-HT levels in old but not in young animals. These observations suggest age-related differences in the response of central NE and 5-HT systems to stress. Ether and the CER procedure led to exaggerated corticosterone responses in the old rats (17.5 and 22 month, respectively). Hippocampal type I but not type II corticosterone receptors were decreased by 47% in the 17.5-month-old rats. Thus, age-related changes in hippocampal corticosterone receptor types do not occur in unison, and the exacerbated corticosterone response to stress precedes the reported down-regulation of hippocampal type II corticosterone receptors in aged rats. Age-related changes were not observed in the concentrations of corticosterone receptors in other brain regions, or in the prolactin response to stress. The old rats, however, evidenced a reduction in the availability of the renin substrate, angiotensinogen, and in stress-induced renin secretion. Immune function was impaired in the old nonstressed rats, and further compromised by exposure to the CER procedure. In comparison to the young control rats, the old nonstressed rats showed an increased percentage of splenic large granular lymphocytes, reduced splenic natural killer cytotoxicity, and impaired Con-A-stimulated splenic T lymphocyte proliferation. Reductions in T splenic cell proliferation and natural killer cytotoxicity were observed in the young rats subjected to the CER paradigm, but not to the same extent as in the old rats. These observations indicate that aging male F344 rats evidence major alterations in basal central monoamine, endocrine and immune functions, and an increased sensitivity of these systems to stress.