PRENATAL COCAINE EXPOSURE INCREASES THE BEHAVIORAL SENSITIVITY OF NEONATAL RAT PUPS TO LIGANDS ACTIVE AT OPIATE RECEPTORS

Offspring of dams given 40 mg/kg cocaine HCl (C40) from gestational day 8-20 (E8-E20), pair-fed dams injected daily with saline (PF), nutritional control dams placed on a 40% cellulose based diet and injected with saline daily (NC), and untreated dams (LC) were examined. Offspring were given morphine (0.0, 0.1, or 0.5 mg/kg SC) on postnatal day 10-11 (P10-11) in Experiment 1, and isolation-induced ultrasonic vocalizations were measured. Planned comparisons indicated that both C40 and NC offspring exhibited a greater sensitivity to the morphine-related decrease in isolation-induced ultrasounds than LC controls. However, the presence of an anesthetized littermate suppressed isolation-induced ultrasounds equally across all groups, with all groups of offspring spending equal amounts of time in physical contact with the littermate. A tail-flick measure of analgesia indicated that PF animals were hyperalgesic relative to the other prenatal treatment groups; however, no differences in sensitivity to morphine were seen across the prenatal groups. In Experiment 2, animals were given the selective delta, [D-Pen2,D-Pen5]-enkephalin (DPDPE), and mu, [D-Alee-NMe-PheGly ol]-enkephalin (DAMGO) agonists ICV and ultrasonic vocalizations were recorded. Results indicated that both C40 and NC offspring were more sensitive to the tow dose of DAMGO; however, because of the profound suppression of vocalizations seen at both doses of DPDPE, potential differences among the prenatal treatment groups in responsiveness to the delta agonist were difficult to detect. The altered psychopharmacological sensitivity of C40 and NC offspring is unlikely to be related simply to the anorexic effects of the treatments, as the PF offspring did not differ from LC offspring in terms of sensitivity to the agonists. The increased sensitivity of C40 offspring to morphine and DAMGO in terms of isolation-induced ultrasounds in the absence of any alteration in sensitivity to morphine-induced analgesia is consistent with previous findings showing that C40 weanlings exhibit increased binding of [H-3]naloxone in forebrain regions such as the nucleus accumbens but no increase in binding in brain stem regions associated with the control of analgesia (13).