Ventrolateral periaqueductal gray matter and the control of tonic immobility

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.