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Rationale: Gestational exposure to cocaine now affects several million people including adolescents and young adults. Whether prenatal drug exposures alter an individual's tendency to take and/or abuse drugs is still a matter of debate. Objectives: This study sought to answer the question 'Does prenatal exposure to cocaine, in a dose-response fashion, alter the rewarding effects of cocaine using a conditioned place preference (CPP) procedure during adolescence in the rat?' Further, we wanted to assess the possible sex differences and the role of being raised in an enriched versus impoverished environment. Methods: Virgin female Sprague-Dawley rats were dosed daily with cocaine at 30 mg/kg (C30), 60 mg/kg (C60), or vehicle intragastrically prior to mating and throughout gestation. Pups were culled, fostered and, on postnatal day (PND) 23, placed into isolation cages or enriched cages with three same-sex littermates and stimulus objects. On PND43-47, CPP was determined across a range of cocaine doses. Results: C30 exposure increased sensitivity to the rewarding effects of cocaine in adolescent males, and being raised in an enriched environment further enhanced this effect. Rats exposed to C60 resembled the controls in cocaine CPP. Overall, females were modestly affected by prenatal cocaine and enrichment. Conclusions: These data support the unique sensitivity of males to the effects of gestational cocaine, that moderate prenatal cocaine doses produce greater effects on developing reward circuits than high doses and that housing condition interacts with prenatal treatment and sex such that enrichment increases cocaine CPP mostly in adolescent males prenatally exposed to moderate cocaine doses. [ABSTRACT FROM AUTHOR]

Rationale: Previous studies have shown that the expression of behavioral sensitization to psychostimulants depends on the age and gender of the animal. Objective: This study was conducted to determine the pattern of behavioral sensitization to repeated administration of methylphenidate (MPD) at three different developmental ages and to assess the response to a cocaine challenge in adulthood. Methods: We gave five daily i.p. injections of 10 or 20 mg kg-1 of MPD (10 MPD, 20 MPD) or saline to male and female rats beginning on postnatal days (PND) 21, 45, or 60. When all groups reached PND 90, rats were challenged with 10 mg kg-1 cocaine. For both MPD administration and cocaine challenge, locomotion and stereotyped behaviors were assessed for 1 h. Results: The 10 MPD dose produced increased locomotion over the other two treatments at all ages. Rats that received 20 MPD showed a decline in locomotion across days with an increase in the time spent in high intensity stereotypy by day 5. Animals treated with 10 MPD showed diverse behavioral responses with adolescents showing somewhat dampened stereotypy than the other two age groups. In response to cocaine, pretreatment with MPD at all ages enhanced the cocaine response and produced qualitatively different patterns of stereotyped behavior for each gender and pretreatment age group. Conclusion: MPD produced clear age-specific sensitization of behavior in rats. Furthermore, exposure to MPD cross-sensitized with cocaine regardless of the age at which MPD exposure occurred with each pretreatment age group showing a unique pattern of responses. [ABSTRACT FROM AUTHOR]

Many studies have shown that developmental cocaine exposure alters brain function and behavior; the present study examined the relationship between brain metabolism and behavioral responses to drug challenge. SKF 82958, a selective D1 dopamine agonist, was administered to preweaning cocaineexposed (50 mg/kg/day) rats and controls at 60 days of age. Deoxyglucose was administered 30 min later, during the peak behavioral response, to measure brain functional activity. Pearson product-moment correlations of behavior (locomotor activity and stereotypic behavior) with rates of glucose metabolism in components of the nigrostriatal and mesolimbic circuits were analyzed. The analysis revealed that under saline-challenge conditions in control animals, rates of metabolism in mesolimbic regions are positively correlated to rates of locomotor activity, whereas in cocaine-treated rats, these correlations were absent. Following SKF challenge, a different pattern was seen; locomotor activity or stereotypic behavior was not correlated with mesolimbic or nigrostriatal metabolism, respectively, in controls but was positively correlated in cocaine-treated rats. Therefore, cocaine exposure during development enhances the coupling of metabolism in components of the mesolimbic and nigrostriatal dopamine systems with the behavioral output associated with these systems under drug-challenge conditions. This may be due to loss of inhibitory influences within the mesolimbic and nigrostriatal systems. Thus, the correlation of behavior and cerebral glucose metabolism provides a unique way of examining the effect of developmental cocaine exposure. [ABSTRACT FROM AUTHOR]