Periaqueductal gray cholecystokinin infusions block morphine-induced disruption of maternal behavior.

Cholecystokinin (CCK) and opiates interaction is critical for maintaining maternal behavior during lactation. Morphine inhibits while CCK restores maternal behavior. Recently we have shown that periaqueductal gray (PAG) is a region critically involved in the opioidergic blockade of maternal behavior. A critical level of morphine-induced activation of the rostral lateral PAG is required to inhibit maternal behavior in lactating rats. Since central CCK injections reverted morphine-induced inhibition of maternal behavior, we tested whether this peptide would act similarly in the PAG. This hypothesis was confirmed in experiments showing that morphine's inhibitory effect on maternal responsiveness was blocked by 1.0 and 0.2 nmol CCK injections into the rostral PAG, but not in nearby regions of the mesencephalic reticular nucleus. To test for possible compensatory changes the CCK2 receptor due to morphine treatments the expression of CCK2 receptor mRNA was evaluated in the PAG. PAG CCK2 receptor cDNA amplification revealed no difference in morphine treated animals. These results broaden understanding of the role played by CCK in the PAG. This CCK action might not depend on changes in its receptor.

Opiate regulation of behavioral selection during lactation.

Treatment of postpartum female rats with morphine inhibits maternal behavior. The same type of treatment stimulates foraging in adult animals. The aim of the present study was to investigate, in lactating rats, the functional role of opioid systems in the choice between caring for pups versus hunting insects. Experiment 1 was designed to test how acute morphine treatment with 3.0 mg/kg interferes with choosing between caring for pups versus predatory behavior. Morphine-treated dams decreased maternal behavior while increasing efficiency in hunting insects. The next step was to test the opioid antagonist naloxone in the same context of maternal versus predatory behavior. Naloxone restored maternal care and reduced hunting in morphine-treated rats. Finally, in order to test the role of endogenous opioidergic stimulation in this scenario, lactating rats were treated with the opioid antagonist naloxone alone. Consistently, naloxone treatment induced a decrease in number of insects captured and an increase in the percentage of animals displaying nursing behavior. These results provide important insight into the role of opioidergic transmission in the regulation of behavioral selection during lactation. The present results suggest that endogenous opioids may stimulate hunting by replacing maternal behavior during lactation.

Morphine treatment during pregnancy modulates behavioral selection in lactating rats.

Previous studies have demonstrated that treatment of postpartum female rats with morphine inhibits maternal behavior and stimulates foraging. Exposure to drugs of abuse may result in a progressive enhancement of their reinforcing effects. Puerperal treatment with morphine leads to reverse tolerance to this drug. The present study investigated whether repeated morphine treatment during late pregnancy may influence the effects of different morphine dosages on behavioral selection in lactating rats. Females were simultaneously exposed to pups and insects, and the choice between taking care of the pups and hunting insects was observed. Female Wistar rats were treated with morphine (3.5 mg/kg/day, subcutaneous [s.c.]) or saline for 5 days beginning on pregnancy day 17. On day 5 of lactation, animals were acutely challenged with morphine (0.5, 1.0, or 1.5 mg/kg, s.c.; MM0.5, MM1.0, and MM1.5 groups, respectively) or saline (MS group) and tested for predatory hunting and maternal behavior. Control groups were pretreated with saline and challenged with morphine (SM0.5, SM1.0, and SM1.5 groups) or saline (SS group). Animals treated with morphine during late pregnancy and acutely challenged with 1.0 mg/kg morphine (MM1.0 group) exhibited significantly decreased maternal behavior and enhanced hunting. This effect was not evident with the 0.5 mg/kg dose. The 1.5 mg/kg morphine dose decreased maternal behavior and increased hunting in both the MM1.5 group and in animals challenged with morphine after previous saline treatment (SM1.5 group). These results provide evidence of plasticity of the opioidergic role in behavioral selection during lactation.