The research in the present proposal examines the involvement of opiates in the normal regulation of maternal behavior and their regulation within the physiological context of pregnancy and lactatin. Experiments are designed to evaluate the hypotheses that: The expression of maternal behavior is regulated by changes in endogenous opioid activity during pregnancy, lactatin and after weaning which are controlled by both endocrine and sensory factors. Specifically, we propose that high levels of opiod activity, i.e. beta endorphin, in the CNS are disruptive to maternal behavior, and that under normal conditions the expression of maternal care is associated with reduced levels of central opiate activity. Using a rat animal model, specific studies evaluate the effects of opiate antagonists on maternal behavior, central sites of endogenous opiate action in the regulation of maternal behavior, and changes in opiate behavioral and neuroendocrine sensitivities during various reproductive and maternal states. The behavioral studies are evaluated in the context of physiological events of pregnancy and lactatin. In the second part of the proposal, endogenous opiate release (beta endorphin) in the brain is assessed using a push-pull perfusion assembly, while central opiate receptors are measured by autoradiography throughout pregnancy and lactation. The involvement of three, behaviorally active hormones secreted in large amounts during pregnancy - progesterone, estradiol and prolactin - in regulating central opiate activity (opiate release in the CNS/receptor concentrations) will then be determined. Finally, in order to account for the diminished opiate sensitivity found in multiparous animals, we will measure the effects of prior parity and reproductive/behavioral experience on CNS opiate activity (opioid release/receptor concentrations). The neurochemical regulation of maternal care and will provide a basis for evaluating the effects of opiate imbalances on mother-young interactions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004291-02
Application #
3209729
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
1989-04-01
Project End
1990-08-31
Budget Start
1990-05-01
Budget End
1990-08-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Mann, P E; Felicio, L F; Bridges, R S (1995) Investigation into the role of cholecystokinin (CCK) in the induction and maintenance of maternal behavior in rats. Horm Behav 29:392-406
Hammer Jr, R P; Bogic, L; Handa, R J (1993) Estrogenic regulation of proenkephalin mRNA expression in the ventromedial hypothalamus of the adult male rat. Brain Res Mol Brain Res 19:129-34
Hammer Jr, R P; Mateo, A R; Bridges, R S (1992) Hormonal regulation of medial preoptic mu-opiate receptor density before and after parturition. Neuroendocrinology 56:38-45
Bridges, R S; Hammer Jr, R P (1992) Parity-associated alterations of medial preoptic opiate receptors in female rats. Brain Res 578:269-74
Mann, P E; Bridges, R S (1992) Neural and endocrine sensitivities to opioids decline as a function of multiparity in the rat. Brain Res 580:241-8
Mateo, A R; Hijazi, M; Hammer Jr, R P (1992) Dynamic patterns of medial preoptic mu-opiate receptor regulation by gonadal steroid hormones. Neuroendocrinology 55:51-8
Mann, P E; Kinsley, C H; Bridges, R S (1991) Opioid receptor subtype involvement in maternal behavior in lactating rats. Neuroendocrinology 53:487-92
Felicio, L F; Mann, P E; Bridges, R S (1991) Intracerebroventricular cholecystokinin infusions block beta-endorphin-induced disruption of maternal behavior. Pharmacol Biochem Behav 39:201-4
Bridges, R S; Numan, M; Ronsheim, P M et al. (1990) Central prolactin infusions stimulate maternal behavior in steroid-treated, nulliparous female rats. Proc Natl Acad Sci U S A 87:8003-7