Effects of prenatal morphine and cocaine on postnatal behaviors and brain neurotransmitters.

There are several possible mechanisms that may explain how psychoactive drugs affect brain and behavioral development. During early development of the CNS, neurotransmitters are thought to act as signals for growth and synaptogenesis (Lauder 1990; Lauder and Krebs 1978; Whitaker-Azmitia et al. 1987). Fetal or early neonatal exposure to opiates or cocaine may cause an overall inhibition of brain growth and development due to inappropriate neural response to hormones and neurotrophic signals during this critical period of CNS development. Because exposure to opiates and cocaine prenatally can alter opioid and catecholamine receptor density and distribution, this in turn could affect the development of neural connections by delaying or accelerating neural outgrowth during fetal and/or postnatal periods (Bardo et al. 1982; Hammer et al. 1989; Spear et al. 1989a, 1989b; Tempel et al. 1988; Tsang and Ng 1980). Another possibility may be alterations in monoamine neurotransmitter levels during gestation. Alterations in levels or distribution of these neurotransmitters may interfere with the mechanisms involved in the establishment of neural connections and behavior patterns. From this and other studies examining the impact of prenatal drug exposure on adult behaviors and brain catecholamine systems, three themes emerge: (1) Exposure of the developing fetus to psychoactive drugs produces long-term alterations in adult behaviors and brain catecholamines, (2) these neurobehavioral and neurochemical alterations are sexually dimorphic, and (3) the hypothalamic catecholamine systems seem particularly vulnerable to prenatal drug exposure. Thus, it is clear that to gain understanding of the impact of prenatal drug exposure on adult brain and behaviors, lifespan studies are essential. These lifespan studies should consider gender as an important variable, because the occurrence of long-term neurobehavioral changes in this author's and other studies strongly suggests that prenatal drug exposure modifies adult male and female brain and behavioral development differently. Additionally, researchers should be aware of the particular sensitivity of the hypothalamus to perturbation by developmental drug exposure. Obviously, understanding the consequences of prenatal drug exposure for the development of the human CNS and behavior is an extremely complicated and difficult task. However, animal models have already proved useful and will be essential to correlate neurochemical and behavioral consequences of prenatal drug exposure with clinical evidence.