Effects of microinjections of neurotoxin AvTx8, isolated from the social wasp Agelaia vicina ( Hymenoptera, Vespidae) venom, on GABAergic nigrotectal pathways

Abstract

Several investigations have provided information that defensive behaviors evoked by stimulation of deep layers of the superior colliculus (dlSC) are subjected to inhibitory nigral modulation. This inhibition is made mainly through GABAergic neurons from substantia nigra, pars reticulata (SNpr), that sends outputs toward neural networks of the deep layers of the superior colliculus and dorsal periaqueductal gray matter involved with the organization of fear-like responses. In this work, we compared the effects of two GABAergic agonists, muscimol and baclofen, with the effect of neurotoxin AvTx8 (1567 Da), isolated from the venom of the social wasp Agelaia vicina, microinjected into SNpr of Rattus norvegicus (Wistar rats) prior to dlSC saline or bicuculline microinjections, considering that wasp venom has some influence on the uptake of GABA and/or glutamate neurotransmitters. GABA A receptor blockade in the dlSC evoked a vigorous escape behavior, expressed by rapid running, jumps and turns, as compared to control. These defensive reactions were maximized after the intranigral GABA A agonism with muscimol, but not after in situ GABA B agonism. Nigral microinjection of AvTx8 induced similar effects to those of baclofen, decreasing the intensity of behavioral defensive reactions caused by GABA A receptor blockade in the dorsal mesencephalon. These findings suggest that AvTx8 has some effects on GABAergic neurotransmission, increasing the activity of the inhibitory nigro-collicular pathways, causing an anti-panic (antiaversive) effect. Therefore, our work suggests AvTx8 as a novel pharmacological tool to study differences between the two types of GABAergic receptors and excitatory amino acid-mediated mechanisms in the brain and brainstem networks.