The work outlined in this proposal will examine further the neurobehavioral consequences of gestational exposure to cocaine administered subcutaneously (s.c.) in Sprague-Dawley rat pups. In work conducted during the previous funding period, psychopharmacological and behavioral evidence was obtained consistent with the hypothesis that gestational cocaine exposure may result in an attenuation in dopamine (DA) activity, at least during the preweaning period. Young offspring exposed gestationally to cocaine were also observed to exhibit cognitive deficits in some but not all conditioning situations. The research outlined in this proposal will investigate further these apparent alterations in DA function and cognitive performance seen early in life following gestational cocaine exposure in Sprague-Dawley rate. Gavid dams will be s.c. injected daily with 10, 20 94 40 mg/kg/3cc cocaine hydrochloride from gestational day 8 (E8) to E20. Control groups include dams similarly injected with 0.9% saline and pair-fed to the 40 mg/kg cocaine dams, as well as non-treated dams. Offspring from all groups will be fostered to surrogate dams on postnatal day 1.
In Specific Aim 1, DA function will be examined in offspring from these prenatal treatment groups throughout ontogeny in terms of assessment of DA metabolism (as an index of DA turnover), responsiveness to pharmacological challenges with apomorphine and haloperidol (using psychopharmacological, neurochemical and hormonal response measures), and examination of DA autoreceptor function.
In Specific Aim 2, studies will examine the circumstances under which cognitive deficits are observed in neonatal, infant, weanling, periadolescent and adult offspring exposed gestationally to cocaine to determine whether observed deficits in conditioning and retention are related to degree of training, the sensory modalities used for conditioned stimuli, the type of unconditioned stimulus used for conditioning, and the type of response measure used for assessment of performance. Studies will also be conducted to assess whether disruptions in cognitive performance seen early in life are related to maturational delays in cognitive development, or to alterations in cognitive function per se. Such animal research examining the neurobehavioral consequences of early cocaine exposure is particularly important at this time, given the recent escalation in the number of human offspring exposed gestationally to cocaine.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004478-07
Application #
2117213
Study Section
Special Emphasis Panel (SRCD (14))
Project Start
1987-09-01
Project End
1995-03-14
Budget Start
1993-09-01
Budget End
1995-03-14
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
State University of NY, Binghamton
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
090189965
City
Binghamton
State
NY
Country
United States
Zip Code
13902
Hecht, G S; Spear, N E; Spear, L P (1999) Changes in progressive ratio responding for intravenous cocaine throughout the reproductive process in female rats. Dev Psychobiol 35:136-45
Campbell, J; Spear, L P (1999) Effects of early handling on amphetamine-induced locomotor activation and conditioned place preference in the adult rat. Psychopharmacology (Berl) 143:183-9
Campbell, J O; Fogarty, J A; Spear, L P (1999) Inhibition of nitric oxide synthesis with L-NAME suppresses isolation-induced ultrasounds in rat pups. Pharmacol Biochem Behav 63:45-53
Katovic, N M; Gresack, J E; Spear, L P (1999) Schedule-induced polydipsia: gender-specific effects and consequences of prenatal cocaine and postnatal handling. Pharmacol Biochem Behav 64:695-704
Hecht, G S; Spear, N E; Spear, L P (1998) Alterations in the reinforcing efficacy of cocaine in adult rats following prenatal exposure to cocaine. Behav Neurosci 112:410-8
Snyder, K J; Katovic, N M; Spear, L P (1998) Longevity of the expression of behavioral sensitization to cocaine in preweanling rats. Pharmacol Biochem Behav 60:909-14
Spear, L P; Campbell, J; Snyder, K et al. (1998) Animal behavior models. Increased sensitivity to stressors and other environmental experiences after prenatal cocaine exposure. Ann N Y Acad Sci 846:76-88
Wood, R D; Tirelli, E; Snyder, K J et al. (1998) Evidence for behavioral sensitization to cocaine in preweanling rat pups. Psychopharmacology (Berl) 138:114-23
Wood, R D; Spear, L P (1998) Prenatal cocaine alters social competition of infant, adolescent, and adult rats. Behav Neurosci 112:419-31
Laviola, G; Wood, R D; Kuhn, C et al. (1995) Cocaine sensitization in periadolescent and adult rats. J Pharmacol Exp Ther 275:345-57

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