Neurotoxicology and Teratology 22 (2000) 421–428 0892-0362/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S0892-0362(99)00080-X Effects of age and gender but not prenatal cocaine on random ratio and delayed spatial alternation responding in rats Vincent P. Markowski a, *, Christopher Cox b , Raymond Preston c , Bernard Weiss d a Department of Psychology, Salem State College, Salem, MA 01970, USA b Department of Biostatistics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA c Department of Psychology, College of Charleston, Charleston, SC 29424, USA d Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA Received 7 September 1999; accepted 23 November 1999 Abstract This investigation employed a longitudinal analysis of rat operant behavior under two different schedules of reinforcement following prenatal exposure to cocaine. Offspring were derived from four maternal exposure groups: 50 mg/kg cocaine, their pair-fed controls, 25 mg/kg cocaine, and freely fed controls. Cocaine was administered via gavage from gestation day 6–20. A maternal fostering procedure was used. Pairs of male and female littermates were assigned to a 7-, 14-, or 21-month cohort and at the appropriate age were trained to re- spond on one lever in a two-lever operant chamber. Reinforcement was delivered with a series of random ratio (RR) schedules where the RR value was increased across sessions. After RR training, animals were examined with a delayed spatial alternation (DSA) procedure in the same chambers. Male offspring responded at higher rates than females during high-probability RR schedules, whereas advancing age was associated with lower response rates during low-probability RR schedules in both males and females. Prenatal cocaine exposure ex- erted only limited effects on RR responding during transition and did not affect DSA behavior. The results of this longitudinal analysis suggest that prenatal cocaine does not exert global or far-reaching learning deficits in prenatally exposed rats. © 2000 Elsevier Science Inc. All rights reserved. Keywords: Aging; Gender; Prenatal cocaine; Sex differences; Random ratio; Delayed spatial alternation; Operant behavior 1. Introduction Early clinical investigations of the effects of prenatal co- caine exposure described a variety of adverse parturition, motor, mood, and state effects [2,3,9,30,31,34]. Most of these investigations examined infants who were 24 months or younger. Although standardized infant developmental measures are relatively weak predictors of long-term cogni- tive outcomes [25], these findings have often been inter- preted as indications that prenatal cocaine produces perma- nent behavioral deficits. Until recently, few long-term follow-ups of prenatally exposed children have been avail- able. Longitudinal examinations of outcomes such as lan- guage development, academic achievement, and classroom behavior suggest that prenatal cocaine is not a potent devel- opmental neurotoxicant [23,24,37]. A wide variety of behavioral models using animal sub- jects has been used in attempts to replicate cocaine exposure effects in infants. A consensus has gradually emerged that prenatal cocaine exposure does not produce global [26] or far-reaching learning deficits in humans or animals [39,46]. Researchers have turned away from the debate concerning prenatal cocaine’s status as a potent behavioral teratogen and are instead beginning to focus on the drug’s effects on animal performance during more complex and narrowly de- fined learning tasks [20,45]. There is some evidence that tasks that require spatial pro- cessing such as the Morris water maze (MWM) are sensi- tive to prenatal cocaine exposure. Although spatial process- ing in humans consists of a number of related cognitive abilities [14], spatial processing in animals is presumably required any time an animal must remember changes in the relative position of important objects. Heyser et al. [21] re- ported that exposed male and female offspring swam a greater distance and required more time to reach the safety platform during the first training trial in the MWM. When * Corresponding author. Tel.: 978-542-6898; fax: 978-542-6834. E-mail address: vincent.markowski@salem.mass.edu (V.P. Markowski).