COCAINE ABUSE: EFFECTS ON BRAIN SEXUAL DIFFERENTIATION

在过去几年中，娱乐性使用可卡因的人数急剧增加

Recreational use of cocaine has increased dramatically in the past few years, resulting in a an increasing number of addicted infants being born to mothers using cocaine during pregnancy. Present evidence indicates that long-term behavioral effects will become evident in these children as they grow older. Preliminary evidence from animal studies indicated that sex related behaviors may be feminized to some degree in males exposed to the drug during perinatal development. The studies we have proposed will seek to determine the extent to which reproductive and non-reproductive sexually dimorphic behaviors are feminized in male rats exposed to cocaine during the prenatal and/or postnatal critical periods for neurobehavioral sexual differentiation. Behaviors to be studied will include masculine and feminine reproductive behavior potentials, scent marking and saccharin preference. The long-term effect of cocaine on the hypothalamic-pituitary-gonadal axis will be examined by studying the pulsatile release of LH, the positive LH feedback response to estrogen and progesterone, morphological studies of sperm, and the pre- and postnatal surge of testosterone. Previous work by ourselves and others has shown that the noradrenergic system is an important modulator of sexual differentiation of the brain. In part, this is due to the ability of norepinephrine to inhibit estradiol incorporation if hypothalamic nuclei. Cocaine enhances noradrenergic activity through its ability to block reuptake at the synapse. Preliminary data described in the application indicate that cocaine can significantly inhibit hypothalamic nuclear incorporation of estradiol on day 1 postnatally. Such an effect appears to be responsible for the incomplete masculinization of behavior we have observed n males exposed prenatally to cocaine. The intermediate and long-term goals of this study are the characterization of the extent to which cocaine will alter the HPG axis and feminize male behavior as well as to begin to define the mechanisms through which this accomplished. It is expected that such information will be of importance in devising eventual treatment strategies to overcome such effects in children prenatally exposed to cocaine.