Foster mother care but not prenatal morphine exposure enhances cocaine self‐administration in young adult male and female rats

Abstract

The present study was designed to investigate cocaine self-administration in adult male and female rats exposed prenatally to morphine. Pregnant dams were injected two times a day with either saline, analgesic doses of morphine or no drug at all (controls) on gestation Days 11-18. One day after birth, litters were cross-fostered such that control dams were paired with one another and their litters were crossed; saline- and morphine-treated dams were paired and half of each saline litter was crossed with half of each morphine litter. Thus, each mother (control, saline, and morphine) raised half of her own and half of the adopted litter. At the age of 60 days, males and females were trained first to lever press for sucrose pellets and then for cocaine. Once the lever-pressing behavior was learned and baseline level of this activity was established, animals received a cocaine (.5 mg/kg per infusion) reward for each correct response on the active lever during the next 9-day session. The data demonstrate that adult control, saline- and morphine-exposed male rats self-administer cocaine at a similar rate independent of their prenatal treatment. Adult female rats self-administer cocaine at a higher rate than male rats. Further, saline- and morphine-exposed females in diestrus self-administer more than females in proestrus phase of the estrous cycle, while control females show no such differences. In addition, fostering induces increase in cocaine self-administration in all groups of male rats regardless of prenatal drug exposure. In females, the only fostering-induced increase is in prenatally saline-exposed female rats raised by morphine-treated foster mother. Thus, our results suggest that the prenatal drug exposure does not induce changes in lever-pressing behavior for cocaine reward in adult male and female rats, but it sensitizes the animals to postnatal stimuli such as gonadal hormones and/or rearing conditions that result in increased drug self-administration.

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

“…Although no differences were reported in females, only one conditioning regimen was examined, and thus it is possible that sensitivity of females to stimulants may be affected under different conditioning parameters. In 268 any case, this sex-dependent effect is interesting in light of other results showing increased vulnerability to cocaine self-administration in male rats, but not female rats, subjected to neonatal stress from crossfostering (Vathy et al, 2007). Increases in locomotor activity to amphetamine also occur in male rats artificially reared in isolation with low levels of maternal-like stimulation, but not with high levels of stimulation (Lovic et al, 2006).…”

Behavioral effects of perinatal opioid exposure

“…Vathy et al studied the later consequences of disrupted maternal care by morphine-treated mothers for offspring (Vathy et al, 2007). The researchers found that disrupted maternal behavior was more important than prenatal drug exposure itself in rewarding cocaine self-administration in adulthood, especially in female offspring.…”

Fostering itself increases nicotine self-administration in young adult male rats

“…Rats with prenatal methamphetamine exposure (5mg/kg/day) show improvement in maturation tests when fostered to drug-naïve dams (Pometlova et al 2009). Similarly, while non-fostered rat offspring with in utero saline or morphine exposure (5mg/kg injection GD11-13, 10mg/kg GD14-18) did not exhibit higher operant response rates for cocaine (0.5mg/kg/inj) compared to controls, fostering itself increased responding for cocaine regardless of prenatal treatment group (Vathy et al 2007). In our previous study, cross-fostering of offspring with prenatal nicotine exposure (3mg/kg/day) did not affect the increase in the dopaminergic response to a nicotine injection.…”