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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA003544-01A3
Application #
3208033
Study Section
(SRC)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Belue, R C; Howlett, A C; Westlake, T M et al. (1995) The ontogeny of cannabinoid receptors in the brain of postnatal and aging rats. Neurotoxicol Teratol 17:25-30
Hutchings, D E (1993) The puzzle of cocaine's effects following maternal use during pregnancy: are there reconcilable differences? Neurotoxicol Teratol 15:281-6
Hutchings, D E; Zmitrovich, A; Brake, S C et al. (1992) Prenatal administration of methadone using the osmotic minipump: effects on maternal and offspring toxicity, growth, and behavior in the rat. Neurotoxicol Teratol 14:65-71
Zmitrovich, A C; Hutchings, D E; Dow-Edwards, D L et al. (1992) Effects of prenatal exposure to cocaine on the rest-activity cycle of the preweanling rat. Pharmacol Biochem Behav 43:1059-64
Hutchings, D E; Brake, S C; Banks, A N et al. (1991) Prenatal delta-9-tetrahydrocannabinol in the rat: effects on auditory startle in adulthood. Neurotoxicol Teratol 13:413-6
Hutchings, D E; Fico, T A; Banks, A N et al. (1991) Prenatal delta-9-tetrahydrocannabinol in the rat: effects on postweaning growth. Neurotoxicol Teratol 13:245-8
Hutchings, D E; Dow-Edwards, D (1991) Animal models of opiate, cocaine, and cannabis use. Clin Perinatol 18:1-22
Hutchings, D E (1990) Issues of risk assessment: lessons from the use and abuse of drugs during pregnancy. Neurotoxicol Teratol 12:183-9
Dow-Edwards, D L; Freed, L A; Fico, T A (1990) Structural and functional effects of prenatal cocaine exposure in adult rat brain. Brain Res Dev Brain Res 57:263-8
Fico, T A; Banks, A N; Hutchings, D E (1990) Prenatal phencyclidine in rats: effects on apomorphine-induced climbing. Pharmacol Biochem Behav 35:93-7

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