Repeated morphine administration during pregnancy attenuates maternal behavior
Introduction
Our previous studies demonstrate that chronic morphine administration to rats during the second half of pregnancy affects the neural and behavioral development of the progeny when examined during development (Schindler et al., 2000, Velı́šková et al., 1999) and in adulthood (Rimanóczy and Vathy, 1995, Šlamberová et al., 2001, Vathy, 2001, Vathy et al., 2000a, Vathy et al., 2000b). Prenatal morphine exposure also alters the onset of puberty and gonadal steroid-dependent adult sexual behavior in male and female rats, but does not affect the birth weight of drug-exposed pups (Vathy et al., 1985, Vathy and Kátay, 1992).
Opioid peptides play an important role in analgesia during second half of pregnancy and parturition (Gintzler, 1980, Hammer and Bridges, 1987, Wardlaw et al., 1982). Exogenous opiate administration during the second half of the pregnancy may also affect the pain system and induces physiological changes in the endogenous opioid system of pregnant rats. These physiological changes may in turn affect maternal behavior. Therefore, the present study tested the hypothesis that repeated morphine administration during the second half of the pregnancy alters maternal behavior during lactation.
Several studies have demonstrated that exogenous opiates, such as morphine, inhibits maternal behavior (Blass et al., 1995, Bridges and Grimm, 1982, Grimm and Bridges, 1983, Kimball, 1979, Mayer et al., 1985, Rubin and Bridges, 1984, Stafisso-Sandoz et al., 1998, Wellman et al., 1997). Mayer et al. (1985) reported that chronic morphine administration beginning on day 9 of pregnancy, decreases placentophagia and/or cleaning pups of umbilical cords during and shortly after parturition. Additionally, Bridges and Grimm (1982) showed that systemic morphine administration, after surgical removal of pups on day 17 of pregnancy, delays the onset of maternal behavior in rats. This effect of morphine can be blocked by a systemic, concurrent administration of the opiate antagonist, naloxone (Bridges and Grimm, 1982). Moreover, morphine administered intracerebroventricularly (icv) (Mann et al., 1991) or into the medial preoptic area of rats (Rubin and Bridges, 1984) blocks maternal behavior. Kinsley et al. (1995) show that there is a maternal aversion to the odor of pups after icv injection of morphine, which is reversible by naloxone.
The above studies show that acute morphine administration during lactation disrupts maternal care. Additionally, chronic morphine administration decreases maternal behavior around parturition (Mayer et al., 1985). However, there are no studies examining how chronic morphine administration during the second half of pregnancy influences subsequent, drug-free maternal behavior throughout the period of lactation. Therefore, two experiments were conducted to assess the effects of chronic morphine administration (2×/day on gestation days 11–18) on maternal behaviors. Experiment 1 examined several maternal and non-maternal activities of lactating, undisturbed rats, and Experiment 2 examined retrieval behavior in morphine- and saline-treated lactating rats. These behaviors in both experiments were examined twice daily. The time of testing was chosen according to Myers et al. (1989). Additionally, knowing that activities are changing according to light/dark cycle (Harker, 1964, Illnerová and Sumová, 1997, Turek, 1994) we were interested in how maternal behavior changes during the light and the dark phase of the reversed light/dark cycle.
Section snippets
General methods
Eight-day pregnant Sprague–Dawley rats were purchased from Taconic Farms (Germantown, NY). Animals were weighed, housed individually in maternity cages, and maintained in a temperature-controlled colony room with free access to food and water on a reversed 14 h (light): 10 h (dark) cycle with lights off at 1100 h. Pregnant rats were randomly assigned to a morphine- (experimental) or a saline-treated (control) group. Morphine sulfate or 0.9% physiological saline injections were administered
Methods
Eight saline- and eight morphine-treated mothers with their pups were observed in two series of tests. A modified method of Myers et al. (1989) was used for assessing maternal behavior. Maternal behavior was observed for 50 min twice a day in the home cage of each mother and her litter. During each 50-minute session, each mother and her litter was observed 10 times for 5 s at 5 min intervals. Twelve types of activities exhibited by the mothers and three nursing positions (see below) were
Methods
Different groups of saline- and morphine-treated mothers (six animals/group) were tested in a retrieval test. The retrieval test was conducted twice a day. Each mother and litter was tested 22 times (11 days×2 sessions/day) between PND 1 (1500 h) and PND 12 (0900 h).
A modified method of Myers et al. (1989) was used for the retrieval tests. All pups were removed from the maternal cage and placed in a separate cage for 5 min. After this brief separation, the entire litter was returned to the
Discussion
Our data demonstrate that repeated morphine treatment on days 11–18 of pregnancy significantly attenuates nursing and active maternal behavior, which replicates the results of others showing inhibitory effects of morphine on maternal behaviors (Blass et al., 1995, Bridges and Grimm, 1982, Grimm and Bridges, 1983, Kimball, 1979, Mayer et al., 1985, Rubin and Bridges, 1984, Stafisso-Sandoz et al., 1998, Wellman et al., 1997). Why morphine-treated mothers show less maternal behavior towards their
Acknowledgements
This study was supported by the grant # DA05833 from NIDA to I.V., the Department of Psychiatry, Albert Einstein College of Medicine, and a Fellowship from Karolinska Institute, Stockholm, Sweden to B.Sz. The procedures for animal experimentation utilized in this report were reviewed and approved by the IACUC.
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