Behavioral characterization of adult male and female rhesus monkeys exposed to cocaine throughout gestation

Abstract

Rationale: In utero cocaine exposure has been associated with alterations in the dopamine (DA) system in monkeys. However, the behavioral outcomes of prenatal cocaine exposure in adulthood are poorly understood.

Objectives: To assess several behavioral measures in 14-year-old rhesus monkeys exposed to cocaine in utero and controls (n = 10 per group).

Materials and methods: For these studies, two unconditioned behavioral tasks, novel object reactivity and locomotor activity, and two conditioned behavioral tasks, response extinction and delay discounting, were examined. In addition, cerebrospinal fluid (CSF) samples were analyzed for concentrations of the monoamine metabolites homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA).

Results: No differences in CSF concentrations of 5-HIAA and HVA, latencies to touch a novel object or locomotor activity measures were observed between groups or sexes. However, prenatally cocaine-exposed monkeys required a significantly greater number of sessions to reach criteria for extinction of food-reinforced behavior than control monkeys. On the delay-discounting task, male prenatally cocaine-exposed monkeys switched preference from the larger reinforcer to the smaller one at shorter delay values than male control monkeys; no differences were observed in females.

Conclusions: These findings suggest that prenatal cocaine exposure results in long-term neurobehavioral deficits that are influenced by sex of the individual.

Fig. 1

a Latency to touch a novel object placed in the monkey's home cage (in seconds). b Number of gridline crossings in a novel environment over 30 min. Values shown are mean±SEM for cocaine-exposed (filled bars) and control (open bars) male and female monkeys

Fig. 2

Number of sessions to extinguish previously food-reinforced responding in male and female monkeys prenatally exposed to cocaine (filled bars) and controls (open bars). Each bar represents mean±SEM values. *p<0.05

Fig. 3

Percentage of trials in which the larger, delayed reinforcer was chosen over the smaller, immediate reinforcer as a function of delay value. Data are from two representative male monkeys, one prenatally cocaine exposed (left panel) and one control (right panel). The delay value at which the curve intersects with the dashed line (50% choice of larger reinforcer) represents the indifference point

Fig. 4

Mean indifference points calculated from delay-discounting procedures for monkeys prenatally exposed to cocaine (filled bars) and controls (open bars). Data are shown for male (left) and female (right) monkeys. Each bar represents mean±SEM values. *p<0.05