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.

Puerperal blockade of cholecystokinin (CCK1) receptors disrupts maternal behavior in lactating rats.

Blockade of cholecystokinin (CCK) receptors potentiates the morphine-induced disruption of maternal behavior. The present study was undertaken to determine whether treatment with lorglumide, a CCK1 antagonist during late pregnancy and early lactation can influence the maternal behavior during lactation. A possible influence of this treatment on general activity was also assessed. Twenty-seven female Wistar rats were pretreated with lorglumide (1.0mg/kg/day; sc) or saline for seven days, starting on the 17th d of pregnancy. After the withdrawal of this treatment, animals were acutely challenged with saline on day 5 and with morphine sulfate (3.0mg/kg; sc) on days 6,10, and 17 of lactation. Groups were pretreated with saline and challenged with saline (group SS) and morphine (group SM), pretreated with lorglumide and challenged with saline (group LS) and morphine (group LM). Animals were also tested for general activity on days 25 and 33 postpartum after an acute challenge with saline and morphine, respectively. Maternal behavior testing began 30 min after the acute injections at which time pups were placed throughout each mother's cage. Latencies for pup retrieval, grouping, crouching and for full maternal behavior responses were scored. Lorglumide pretreatment inhibited maternal behavior of LS vs SS group and potentiated the morphine-induced disruption of this behavior in all days of test (LM vs SM group). No significant differences were found in general activity on days 25 and 33 postpartum. These data suggest that blockade of CCK1 receptors during puerperal period has long-term implications for maternal behavior.

A role for the periaqueductal grey in opioidergic inhibition of maternal behaviour.

Opiates are known to be involved in the regulation of various events surrounding parturition and lactation, such as maternal behaviour in rats. The onset of this behaviour has been closely linked to opiate action in the medial pre-optic area, where administration of morphine disrupts maternal behaviour during lactation. By combining the use of Fos protein immunohistochemical detection and pharmacological manipulations, in the present paper we show that the periaqueductal grey (PAG) is another region critically involved in the opioidergic blockade of maternal behaviour. According to our observations, a critical level of morphine-induced activation of the rostral lateral PAG appears to be required to inhibit maternal behaviour in lactating rats. This hypothesis was further confirmed in experiments showing that morphine's inhibitory effect on maternal responsiveness was blocked by unilateral naloxone injection into the rostral PAG, but not into nearby regions of the mesencephalic reticular nucleus. Therefore, only a partial inhibition of the opiate's effect on the rostral PAG was needed to block the inhibitory effect of morphine on maternal behaviour. Further studies are needed to ascertain whether the rostral lateral PAG plays a role in the natural onset of maternal behaviour, playing a complementary role to the medial pre-optic area, or merely inhibits maternal behaviour in response to this specific pharmacological challenge. Conversely, the present findings may well reflect a more general role of the PAG, seemingly providing an important piece of information for proposing a hitherto unexplored concept of the PAG as an important centre for the selection of adaptive behavioural responses.