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.
Lorens
S A
SA
Department of Pharmacology, Loyola University Chicago Medical Center, Maywood, Illinois 60153.
Guschwan
M
M
Hata
N
N
van de Kar
L D
LD
Walenga
J M
JM
Fareed
J
J
D000375:Aging / Q000187:drug effects* / Q000523:psychology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002421:Caudate Nucleus / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects*; D005239:Fear / Q000187:drug effects; D006496:Heparinoids / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology; D010807:Physical Endurance / Q000187:drug effects; D011699:Putamen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013312:Stress, Physiological / Q000503:physiopathology
D006496:Heparinoids; D016627:Oxidopamine; D004298:Dopamine; D003345:Corticosterone