Flight induced by microinjection of D-tubocurarine or alpha-bungarotoxin into medial hypothalamus or periaqueductal gray matter: cholinergic or GABAergic mediation?

Microinjections of various doses (50-300 ng) of the nicotinic antagonist D-tubocurarine (TUBO) into the rat's medial hypothalamus (MH) or dorsal periaqueductal gray (PAG) produced flight reactions characterized by jumps. Two different types of flight reactions were produced depending on whether the drug was injected into the MH or into the PAG. MH injections provoked an increase in both locomotor activity and rearing together with well-oriented jumps. PAG injections provoked either freezing reactions or running with explosive jumps, but no increase in rearing. In addition, the rat exhibited an asymmetry in responsiveness to tactile stimulation. These reactions also differed depending on whether the drug was injected into the dorsal or ventral PAG. Behavioral reactions similar to those produced by TUBO were also produced by microinjection of the GABA receptor antagonist bicuculline into the same brain sites. Among the 4 putative cholinergic antagonists tested under the same conditions only alpha-bungarotoxin produced effects that were qualitatively similar to those induced by D-tubocurarine or bicuculline. Gallamine and hemicholinium produced tremor when injected into sites located near the ventricular system at either the MH or the PAG level, while vocalizations were only produced by PAG injections. Hexamethonium produced no marked effect. The hypothesis that flight reactions induced by D-tubocurarine or alpha-bungarotoxin do not result from their antinicotinic action but rather from a direct effect on GABAergic transmission is discussed.