Delta-9 tetrahydrocannabinol (THC) will be administered to gravid rats during the last two weeks of gestation to study neurobehavioral effects in the offspring. THC will be suspended in Tween 80 and saline and administered subcutaneously. If preliminary studies find Tween 80 to be toxic, an alternative suspension system will be substituted. To select a dose-range of THC that will not produce excessive maternal toxicity, preliminary studies will compare three dose-levels. Standard measures will be used to assess reproductive toxicity including maternal weight gain, birthweight, viability, resorptions and postnatal mortality. For the study of postnatal neurobehavioral effects, in addition to the three THC dose-level groups, one control group will be pair-fed to the highest THC dose-level group and administered the vehicle. A nontreated control group will be left undisturbed throughout pregnancy. At birth, all treated and control litters will be weighed, culled and fostered to surrogate dams. Behavioral assessment during the postnatal period will include 1) ontogeny of locomotor activity, 2) measurement of the rest-activity cycle and 3) determination of electroconvulsive shock seizure thresholds. In addition, brains from treated and control offspring will be assayed to determine cell number, cell size and effects on catecholamines. To determine possible long-term behavioral effects, differences in activity level will be assessed using the open-field at 21-23, 40-45 and 60-65 days of age. During adulthood, animals will be lever-trained and tested on several operant tasks including responding on a variable interval reinforcement schedule and acquisition and performance of an S+, S-discrimination task.
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