Effects of AZT, ddC, and d4T on Memory in Male and Female Rats
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD BETHESDA United States
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Some anti-HIV medications exert behavioral and neurotoxic side effects that deleteriously affect quality of life. The present research examined the effects of three anti-IDV medications - AZT, ddC, and d4T- on memory in Sprague-Dawley male and female rats. Memory was chosen as the dependent variable because it is an important psychological construct, its profound effects on quality of life, and its relationship to medication compliance. Three experiments used retention of the active avoidance shuttle box performance as an index of memory. Experiment 1 N60 found that males dosed with medication performed significantly slower Le., demonstrating impaired memory function than females. Females dosed with AZT or ddC performed significantly faster on the second day, compared to the first day, of testing. Experiment 2 N80 examined acute administration of d4T in male and female rats. All subjects showed a decrease in latencies over time. There were no significant drug effects. Experiment 3 N84 examined effects of long-term administration, and subsequent cessation, on latencies of male and female rats chronically dosed with d4T. There were no gender or drug effects in day one or day two of testing. Upon cessation of the drug, animals that had received drug performed more poorly than control animals. Males latencies were longer than female latencies when comparing the 1.0 mgkg and 3.0 mgkg levels to saline. Male latencies were significantly longer than saline at the 0.1 mgkg drug level. Overall, male rats were more sensitive to the effects of ddC and AZT on memory. Dosage regimens of d4T, acute vs. chronic, did not have an effect on memory as measured by performance in the active avoidance shuttle box paradigm. However, effects of d4T on shuttle box performance were revealed after cessation of the drug.
- Medicine and Medical Research