Gender differences in the intravenous self-administration of mu opiate agonists
Section snippets
Humane care of laboratory animals
All of the experiments and protocols employed in these studies were reviewed and approved by the Institutional Animal Care and Use Committee.
Materials
Sprague–Dawley male and female rats, 60 days of age, were purchased from Harlan Sprague Dawley (Indianapolis, IN). Self-administration catheter sets were purchased from Med-Associates (Lafayette, IN). Heroin and morphine-sulfate were generously provided by the National Institute on Drug Abuse (Bethesda, MD).
IV self-administration
Male and female rats, which were food restricted
Effects of opiates on operant rates of responding for food reinforcement
To ascertain whether opiates stimulated or suppressed operant behavior in general, as opposed to a specific effect on self-administration rates, 12 female and 12 male rats were trained to self-administer food pellets using an FR1 schedule of reinforcement; 20 reinforcements were possible during each 40-min daily session. Once the behavior was acquired (>85% correct responses), the rats were shifted to a variable interval (VI) schedule of reinforcement (VI—120 s). In this paradigm, a light above
Dose–response analysis
Fig. 1A and B shows the number of infusions taken in the heroin dose–response analysis. The data are presented as number of infusion versus dose of heroin, expressed as micrograms heroin/200 μl infusion (panel A, which was the standard infusion volume for both males and females), and numbers of infusions versus heroin dose expressed as micrograms/kilogram/infusion to adjust for the large gender differences in body weight (panel B). As can be seen, the number of infusions taken by females was
Discussion
The results of these studies indicate that strong gender differences exist in the IV self-administration of two mu opiate agonists—heroin and morphine. At a standard fixed ratio (FR), females consumed significantly greater amounts of heroin and morphine than did males in a dose-dependent fashion. In addition, females also showed much higher breakpoints for morphine self-administration than did males. These results appear to reflect differences in the potency or efficacy of heroin and morphine
Acknowledgements
This research was supported by a grant from the National Institute on Drug Abuse (TJC), DA-03839.
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