A Role for the Periaqueductal Gray in Switching Adaptive Behavioral Responses

Abstract

Previous studies suggested a role for the rostral lateral periaqueductal gray (PAG) in the inhibition of maternal behavior induced by low doses of morphine in dams with previous morphine experience. In the present study, we first showed that unilateral NMDA lesions placed in this particular PAG region prevented the morphine-induced inhibition of maternal behavior in previously morphine-sensitized dams. As suggested by previous Fos data on the PAG, predatory hunting appears as a likely candidate to replace maternal behavior in the morphine-treated dams. By testing saline-and morphine-treated dams with live cockroaches only, we have presently shown that morphine challenge increased insect hunting. Moreover, morphine-and saline-treated dams were also observed in an environment containing pups and roaches. Although most of the saline-treated animals displayed active nursing and only occasionally presented insect hunting, all of the morphine-treated animals ignored the pups and avidly pursued and caught the roaches. We next questioned whether the rostral lateral PAG would be involved in this behavioral switch. Our results showed that unilateral lesions of the rostral lateral PAG, but not other parts of the PAG, partially impaired predatory hunting and restored part of the maternal response. Moreover, bilateral lesions of the rostral lateral PAG produced even more dramatic effects in inhibiting insect hunting and restoring maternal behavior. The present findings indisputably show that the rostral lateral PAG influences switching from maternal to hunting behavior in morphinetreated dams, thus supporting a previously unsuspected role for the PAG in selecting adaptive behavioral responses.

Morphine infusions into the rostrolateral periaqueductal gray affect maternal behaviors

“…At the end of pregnancy, unilateral cytotoxic lesions induced by N-methyld-aspartate (NMDA) in the same area had reversed morphine-inhibition of maternal behaviors when dams were tested only with pups (20). In the present study, a single unilateral infusion of morphine into the rlPAG was sufficient to inhibit parameters involved in maternal behaviors.…”

“…Data are reported as median and interquartile ranges (Q 1 -Q 3 ). Regarding the latency parameters, we attributed scores for statistical analysis, excluding latency for locomotor behavior to explore the home cage, as follows: 1 = 0-300 s, 2 = 301-600 s, 3 = 601-900 s, 4 = 901-1200 s, 5 = 1201-1500 s, 6 = 1501-1800 s, 7 = >1801 s (20). This transformation allowed us to include in our analysis those animals that did not perform the behavioral parameter within the 30-min observation period.…”

Neural mechanisms of predatory aggression in rats—Implications for abnormal intraspecific aggression

“…Here we found that muricidal attacks were accompanied by a dominantly ventral activation of the PAG. Congruent findings were obtained in the cockroach-hunting model [27,28,51]. A comparison of cockroach hunting-and muricide-induced c-Fos activity also suggests a rostrocaudal heterogeneity of the PAG and a potential role of rostral regions in the switch between intraspecific and predatory attack patterns.…”

Social defeat, a paradigm of depression in rats that elicits 22-kHz vocalizations, preferentially activates the cholinergic signaling pathway in the periaqueductal gray

“…Whereas the ventral PAG appears to be involved in animal models of depression [73], the dorsal PAG has been implicated in animal models of anxiety [59]. However, it is important to note that the PAG plays a key role in many other emotional / motivational states besides negative affective ones such as maternal and predatory behavior [76].…”

“…The key neurotransmitter for the generation of this vocalization is acetylcholine [10], and the PAG is part of the essential neural circuit of these vocalizations [35]. Although speculative, changes in acetylcholinesterase T subunit may reflect a change in affective set point by increasing tonic levels of acetylcholine or serve as a switching mechanism from low to high defensive behavioral responses [76], and therapies that alter the expression or activity of this subunit may provide novel treatment for depressive disorders.…”