Modulation by morphine of aversive-like behavior induced by GABAergic blockade in periaqueductal gray or medial...

Pretreatment with "analgesic" doses (15 nmoles) of morphine injected either into the periaqueductal gray (PAG) or into the medial hypothalamus (MH) were found to modulate flight behavior elicited by bicuculline injected into the same brain sites. When injected into the MH, morphine always suppressed bicuculline-induced flight, while PAG injections paradoxically either suppressed or facilitated the behavioral effects produced by bicuculline. Whenever a facilitation of the bicuculline-induced effects had been observed following pretreatment with 15 nmoles of morphine into the PAG, the infusion of lower doses (6 nmoles) did no longer induce facilitation but clear suppression. In those animals that had shown suppression of the aversive-like effects of bicuculline following the same 15 nmoles pretreatment, infusion of higher doses (24 nmoles) of morphine into the PAG still produced the same kind of suppression. And yet, when injected into the PAG, very high doses of morphine (50 nmoles) were found to induce, by themselves, flight behavior known as explosive motor behavior. In contrast, such high doses of morphine never induced comparable explosive motor behavior when injected into the MH. These data can be explained by the involvement of different types of receptors in the neural mechanisms subserving and controlling the generation of aversion in periventricular brain regions (PAG and MH).