Adolescent cocaine and injection stress effects on the estrous cycle

Chronic cocaine exposure during critical periods of development induces sho rt- and long-term effects. During the pubertal period, the hypothalamic-pit uitary-gonadal (IBG) axis undergoes many dynamic changes. The present study investigated whether chronic periadolescent cocaine alters reproductive ma turity in the rat. Sixty female Long-Evans hooded rats were randomly assign ed to one of three conditions (20 mg cocaine/kg/day, saline injected and un injected), for dosing from postnatal day 21 (P21) through P60. Several indi cators of reproductive maturation and functioning were assessed during and following treatment. Cocaine exposure had no effect on the onset of puberty or on the date of first ovulation. The number of proestrus-estrus transiti ons was significantly lower in cocaine-exposed females compared to uninject ed females, but not compared to saline-injected controls. This reduction wa s observed during exposure to cocaine, as well as after the cessation of in jections. During the dosing period cocaine-exposed rats also exhibited a gr eater number of cycles that had no clear P-E transition than did UN subject s; this effect disappeared once injections stopped. These alterations sugge st immediate, and possibly persisting, alterations in the control of ovulat ion after chronic cocaine exposure throughout adolescence. Interestingly du ring the injection period, the saline-injected females had a significantly greater number of diestrus days compared to uninjected and cocaine-injected animals, as well as a lower proportion of regular 4- and 5-day cycles. The se differences disappeared once injections stopped. These results suggest a stress-induced irregularity of the estrous cycle, possibly attenuated by c ocaine and recoverable after exposure. The present findings indicate that t he HPG axis is susceptible to short-term, and possibly to long-term, altera tions induced by cocaine exposure throughout the adolescent period. (C) 200 0 Elsevier Science Inc. All rights reserved.