Tonic immobility is an inborn defensive behavior characterized by a tempora
ry state of profound and reversible motor inhibition elicited by some forms
of physical restraint. The periaqueductal gray matter (PAG) contains neura
l circuits involved in descending pain modulation, as well as in the modula
tion of Tl. We have reported previously that the cholinergic stimulation of
the ventrolateral PAG increases the duration of Tl in guinea pigs. In the
present study, we attempted to characterize further the modulation of Tl by
pharmacological alteration of the neurochemistry of the ventrolateral PAG
circuitry. We observed that both cholinergic (carbachol, 5.4 nmol/0.2 mu l)
and opioidergic stimulations (morphine, 4.48 nmol/0.2 mu l) of the ventrol
ateral PAG increase the duration of Tl and that these effects can be revers
ed by pre-treatment with naloxone (2.74 nmol/0.2 mu l). Our results also sh
owed that microinjection of the GABAergic agonist muscimol (1, 0.5, and 0.2
6 nmol/0.2 mu l) decreased the duration of Tl episodes, while microinjectio
n of the GABAergic antagonist bicuculline (1 nmol/mu l) increased it. Moreo
ver, we observed that preadministration of muscimol (0.13 nmol/0.2 mu l) at
a dose that had no effect per se at this site antagonized the potentiating
effect of morphine. Our results suggest that this modulation of Tl from th
e ventrolateral PAG circuitry is accomplished by a complex interaction of c
holinergic, opioidergic, and GABAergic mechanisms, similar to that proposed
for descending antinociceptive circuits. (C) 1999 Elsevier Science Inc.