Developmental changes in the behavioral and autonomic effects of kappa opioid receptor stimulation of the midbrain periaqueductal gray.

Kappa opioid receptors stimulation with U50,488 is known to modulate behaviors during the early postnatal period, but the specific neuroanatomical locus of many of these effects is unexplored. In the present study, we infused U50,488 into the midbrain periaqueductal gray (PAG) and investigated the effects of this drug on behavior and heart rate of 1-, 2-, and 3-week-old rats. U50,488 increased activity most potently in 1- and 2-week-old subjects. Ultrasonic vocalization (USV) production was increased in 1-week-old subjects, but not in 2- or 3-week-old pups. Heart rate changes were similarly seen in younger aged subjects. At 1 week, U50,488 decreased heart rate, but at 2 weeks it increased heart rate. There was no effect of this drug on heart rate at 3 weeks. At 1 week, USVs were more potently elicited from dorsal than lateral PAG infusion sites. No other site-specific effects within the PAG were seen. The age-related decline in behavioral effects elicited by U50,488 is consistent with other published reports, and to the extent that kappa receptor activity mediates infant separation responses, implicates the PAG as a modulator of those responses. 2004 Wiley Periodicals, Inc